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MS in Stem Cell Biology and Regenerative Medicine

Sunday, November 7th, 2021

Discover the future of medicine

The Master of Science degree program invites you to chart the course for the medicine of the futureregenerative medicine. This is one of the first masters programs in stem cell biology and regenerative medicine in the United States.

Our one-year program offers courses in cutting-edge biomedical science, including developmental biology, human embryology, regenerative medicine, and the translational and therapeutic aspects of stem cell technology. The program also provides practical hands-on laboratory experience with the growth and differentiation of stem cells. Although not required, students are encouraged to engage in laboratory research during the year, with one of the 80+ lab groups that constitute USC Stem Cell. At the completion of the first year, students may informally continue to conduct research in their labs after receiving the MS diploma, or can petition to continue research with a guided and structured second research year culminating in a capstone thesis project.

After completing this program, you will be poised to apply to medical or PhD programs, enter the growing stem cell pharmaceutical domain, or engage in other academic, clinical or business efforts. You will possess a unique understanding of how the bodys own developmental and repair mechanisms can restore damaged cells, tissues and organsproviding new opportunities to treat conditions ranging from blindness to cancer, from organ failure to HIV/AIDS.

To apply, visit gradadm.usc.edu.

Please note that the application portal for Fall 2022 will open October 15th, 2021. The deadline to apply will be April 1st, 2022.

For questions, e-mail us at scrm@usc.edu or call (323) 865 1266.

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MS in Stem Cell Biology and Regenerative Medicine

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Stem Cells Applications in Regenerative Medicine and …

Sunday, November 7th, 2021

Int J Cell Biol. 2016; 2016: 6940283.

Department of Biological Sciences, Indian Institute of Science Education and Research (IISER), Bhopal, Madhya Pradesh 462066, India

Department of Biological Sciences, Indian Institute of Science Education and Research (IISER), Bhopal, Madhya Pradesh 462066, India

Academic Editor: Paul J. Higgins

Received 2016 Mar 13; Accepted 2016 Jun 5.

This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Regenerative medicine, the most recent and emerging branch of medical science, deals with functional restoration of tissues or organs for the patient suffering from severe injuries or chronic disease. The spectacular progress in the field of stem cell research has laid the foundation for cell based therapies of disease which cannot be cured by conventional medicines. The indefinite self-renewal and potential to differentiate into other types of cells represent stem cells as frontiers of regenerative medicine. The transdifferentiating potential of stem cells varies with source and according to that regenerative applications also change. Advancements in gene editing and tissue engineering technology have endorsed the ex vivo remodelling of stem cells grown into 3D organoids and tissue structures for personalized applications. This review outlines the most recent advancement in transplantation and tissue engineering technologies of ESCs, TSPSCs, MSCs, UCSCs, BMSCs, and iPSCs in regenerative medicine. Additionally, this review also discusses stem cells regenerative application in wildlife conservation.

Regenerative medicine, the most recent and emerging branch of medical science, deals with functional restoration of specific tissue and/or organ of the patients suffering with severe injuries or chronic disease conditions, in the state where bodies own regenerative responses do not suffice [1]. In the present scenario donated tissues and organs cannot meet the transplantation demands of aged and diseased populations that have driven the thrust for search for the alternatives. Stem cells are endorsed with indefinite cell division potential, can transdifferentiate into other types of cells, and have emerged as frontline regenerative medicine source in recent time, for reparation of tissues and organs anomalies occurring due to congenital defects, disease, and age associated effects [1]. Stem cells pave foundation for all tissue and organ system of the body and mediates diverse role in disease progression, development, and tissue repair processes in host. On the basis of transdifferentiation potential, stem cells are of four types, that is, (1) unipotent, (2) multipotent, (3) pluripotent, and (4) totipotent [2]. Zygote, the only totipotent stem cell in human body, can give rise to whole organism through the process of transdifferentiation, while cells from inner cells mass (ICM) of embryo are pluripotent in their nature and can differentiate into cells representing three germ layers but do not differentiate into cells of extraembryonic tissue [2]. Stemness and transdifferentiation potential of the embryonic, extraembryonic, fetal, or adult stem cells depend on functional status of pluripotency factors like OCT4, cMYC, KLF44, NANOG, SOX2, and so forth [35]. Ectopic expression or functional restoration of endogenous pluripotency factors epigenetically transforms terminally differentiated cells into ESCs-like cells [3], known as induced pluripotent stem cells (iPSCs) [3, 4]. On the basis of regenerative applications, stem cells can be categorized as embryonic stem cells (ESCs), tissue specific progenitor stem cells (TSPSCs), mesenchymal stem cells (MSCs), umbilical cord stem cells (UCSCs), bone marrow stem cells (BMSCs), and iPSCs (; ). The transplantation of stem cells can be autologous, allogenic, and syngeneic for induction of tissue regeneration and immunolysis of pathogen or malignant cells. For avoiding the consequences of host-versus-graft rejections, tissue typing of human leucocyte antigens (HLA) for tissue and organ transplant as well as use of immune suppressant is recommended [6]. Stem cells express major histocompatibility complex (MHC) receptor in low and secret chemokine that recruitment of endothelial and immune cells is enabling tissue tolerance at graft site [6]. The current stem cell regenerative medicine approaches are founded onto tissue engineering technologies that combine the principles of cell transplantation, material science, and microengineering for development of organoid; those can be used for physiological restoration of damaged tissue and organs. The tissue engineering technology generates nascent tissue on biodegradable 3D-scaffolds [7, 8]. The ideal scaffolds support cell adhesion and ingrowths, mimic mechanics of target tissue, support angiogenesis and neovascularisation for appropriate tissue perfusion, and, being nonimmunogenic to host, do not require systemic immune suppressant [9]. Stem cells number in tissue transplant impacts upon regenerative outcome [10]; in that case prior ex vivo expansion of transplantable stem cells is required [11]. For successful regenerative outcomes, transplanted stem cells must survive, proliferate, and differentiate in site specific manner and integrate into host circulatory system [12]. This review provides framework of most recent (; Figures ) advancement in transplantation and tissue engineering technologies of ESCs, TSPSCs, MSCs, UCSCs, BMSCs, and iPSCs in regenerative medicine. Additionally, this review also discusses stem cells as the tool of regenerative applications in wildlife conservation.

Promises of stem cells in regenerative medicine: the six classes of stem cells, that is, embryonic stem cells (ESCs), tissue specific progenitor stem cells (TSPSCs), mesenchymal stem cells (MSCs), umbilical cord stem cells (UCSCs), bone marrow stem cells (BMSCs), and induced pluripotent stem cells (iPSCs), have many promises in regenerative medicine and disease therapeutics.

ESCs in regenerative medicine: ESCs, sourced from ICM of gastrula, have tremendous promises in regenerative medicine. These cells can differentiate into more than 200 types of cells representing three germ layers. With defined culture conditions, ESCs can be transformed into hepatocytes, retinal ganglion cells, chondrocytes, pancreatic progenitor cells, cone cells, cardiomyocytes, pacemaker cells, eggs, and sperms which can be used in regeneration of tissue and treatment of disease in tissue specific manner.

TSPSCs in regenerative medicine: tissue specific stem and progenitor cells have potential to differentiate into other cells of the tissue. Characteristically inner ear stem cells can be transformed into auditory hair cells, skin progenitors into vascular smooth muscle cells, mesoangioblasts into tibialis anterior muscles, and dental pulp stem cells into serotonin cells. The 3D-culture of TSPSCs in complex biomaterial gives rise to tissue organoids, such as pancreatic organoid from pancreatic progenitor, intestinal tissue organoids from intestinal progenitor cells, and fallopian tube organoids from fallopian tube epithelial cells. Transplantation of TSPSCs regenerates targets tissue such as regeneration of tibialis muscles from mesoangioblasts, cardiac tissue from AdSCs, and corneal tissue from limbal stem cells. Cell growth and transformation factors secreted by TSPSCs can change cells fate to become other types of cell, such that SSCs coculture with skin, prostate, and intestine mesenchyme transforms these cells from MSCs into epithelial cells fate.

MSCs in regenerative medicine: mesenchymal stem cells are CD73+, CD90+, CD105+, CD34, CD45, CD11b, CD14, CD19, and CD79a cells, also known as stromal cells. These bodily MSCs represented here do not account for MSCs of bone marrow and umbilical cord. Upon transplantation and transdifferentiation these bodily MSCs regenerate into cartilage, bones, and muscles tissue. Heart scar formed after heart attack and liver cirrhosis can be treated from MSCs. ECM coating provides the niche environment for MSCs to regenerate into hair follicle, stimulating hair growth.

UCSCs in regenerative medicine: umbilical cord, the readily available source of stem cells, has emerged as futuristic source for personalized stem cell therapy. Transplantation of UCSCs to Krabbe's disease patients regenerates myelin tissue and recovers neuroblastoma patients through restoring tissue homeostasis. The UCSCs organoids are readily available tissue source for treatment of neurodegenerative disease. Peritoneal fibrosis caused by long term dialysis, tendon tissue degeneration, and defective hyaline cartilage can be regenerated by UCSCs. Intravenous injection of UCSCs enables treatment of diabetes, spinal myelitis, systemic lupus erythematosus, Hodgkin's lymphoma, and congenital neuropathies. Cord blood stem cells banking avails long lasting source of stem cells for personalized therapy and regenerative medicine.

BMSCs in regenerative medicine: bone marrow, the soft sponge bone tissue that consisted of stromal, hematopoietic, and mesenchymal and progenitor stem cells, is responsible for blood formation. Even halo-HLA matched BMSCs can cure from disease and regenerate tissue. BMSCs can regenerate craniofacial tissue, brain tissue, diaphragm tissue, and liver tissue and restore erectile function and transdifferentiation monocytes. These multipotent stem cells can cure host from cancer and infection of HIV and HCV.

iPSCs in regenerative medicine: using the edge of iPSCs technology, skin fibroblasts and other adult tissues derived, terminally differentiated cells can be transformed into ESCs-like cells. It is possible that adult cells can be transformed into cells of distinct lineages bypassing the phase of pluripotency. The tissue specific defined culture can transform skin cells to become trophoblast, heart valve cells, photoreceptor cells, immune cells, melanocytes, and so forth. ECM complexation with iPSCs enables generation of tissue organoids for lung, kidney, brain, and other organs of the body. Similar to ESCs, iPSCs also can be transformed into cells representing three germ layers such as pacemaker cells and serotonin cells.

Stem cells in wildlife conservation: tissue biopsies obtained from dead and live wild animals can be either cryopreserved or transdifferentiated to other types of cells, through culture in defined culture medium or in vivo maturation. Stem cells and adult tissue derived iPSCs have great potential of regenerative medicine and disease therapeutics. Gonadal tissue procured from dead wild animals can be matured, ex vivo and in vivo for generation of sperm and egg, which can be used for assistive reproductive technology oriented captive breeding of wild animals or even for resurrection of wildlife.

Application of stem cells in regenerative medicine: stem cells (ESCs, TSPSCs, MSCs, UCSCs, BMSCs, and iPSCs) have diverse applications in tissue regeneration and disease therapeutics.

For the first time in 1998, Thomson isolated human ESCs (hESCs) [13]. ESCs are pluripotent in their nature and can give rise to more than 200 types of cells and promises for the treatment of any kinds of disease [13]. The pluripotency fate of ESCs is governed by functional dynamics of transcription factors OCT4, SOX2, NANOG, and so forth, which are termed as pluripotency factors. The two alleles of the OCT4 are held apart in pluripotency state in ESCs; phase through homologues pairing during embryogenesis and transdifferentiation processes [14] has been considered as critical regulatory switch for lineage commitment of ESCs. The diverse lineage commitment potential represents ESCs as ideal model for regenerative therapeutics of disease and tissue anomalies. This section of review on ESCs discusses transplantation and transdifferentiation of ESCs into retinal ganglion, hepatocytes, cardiomyocytes, pancreatic progenitors, chondrocytes, cones, egg sperm, and pacemaker cells (; ). Infection, cancer treatment, and accidents can cause spinal cord injuries (SCIs). The transplantation of hESCs to paraplegic or quadriplegic SCI patients improves body control, balance, sensation, and limbal movements [15], where transplanted stem cells do homing to injury sites. By birth, humans have fixed numbers of cone cells; degeneration of retinal pigment epithelium (RPE) of macula in central retina causes age-related macular degeneration (ARMD). The genomic incorporation of COCO gene (expressed during embryogenesis) in the developing embryo leads lineage commitment of ESCs into cone cells, through suppression of TGF, BMP, and Wnt signalling pathways. Transplantation of these cone cells to eye recovers individual from ARMD phenomenon, where transplanted cone cells migrate and form sheet-like structure in host retina [16]. However, establishment of missing neuronal connection of retinal ganglion cells (RGCs), cones, and PRE is the most challenging aspect of ARMD therapeutics. Recently, Donald Z Jacks group at John Hopkins University School of Medicine has generated RGCs from CRISPER-Cas9-m-Cherry reporter ESCs [17]. During ESCs transdifferentiation process, CRIPER-Cas9 directs the knock-in of m-Cherry reporter into 3UTR of BRN3B gene, which is specifically expressed in RGCs and can be used for purification of generated RGCs from other cells [17]. Furthermore, incorporation of forskolin in transdifferentiation regime boosts generation of RGCs. Coaxing of these RGCs into biomaterial scaffolds directs axonal differentiation of RGCs. Further modification in RGCs generation regime and composition of biomaterial scaffolds might enable restoration of vision for ARMD and glaucoma patients [17]. Globally, especially in India, cardiovascular problems are a more common cause of human death, where biomedical therapeutics require immediate restoration of heart functions for the very survival of the patient. Regeneration of cardiac tissue can be achieved by transplantation of cardiomyocytes, ESCs-derived cardiovascular progenitors, and bone marrow derived mononuclear cells (BMDMNCs); however healing by cardiomyocytes and progenitor cells is superior to BMDMNCs but mature cardiomyocytes have higher tissue healing potential, suppress heart arrhythmias, couple electromagnetically into hearts functions, and provide mechanical and electrical repair without any associated tumorigenic effects [18, 19]. Like CM differentiation, ESCs derived liver stem cells can be transformed into Cytp450-hepatocytes, mediating chemical modification and catabolism of toxic xenobiotic drugs [20]. Even today, availability and variability of functional hepatocytes are a major a challenge for testing drug toxicity [20]. Stimulation of ESCs and ex vivo VitK12 and lithocholic acid (a by-product of intestinal flora regulating drug metabolism during infancy) activates pregnane X receptor (PXR), CYP3A4, and CYP2C9, which leads to differentiation of ESCs into hepatocytes; those are functionally similar to primary hepatocytes, for their ability to produce albumin and apolipoprotein B100 [20]. These hepatocytes are excellent source for the endpoint screening of drugs for accurate prediction of clinical outcomes [20]. Generation of hepatic cells from ESCs can be achieved in multiple ways, as serum-free differentiation [21], chemical approaches [20, 22], and genetic transformation [23, 24]. These ESCs-derived hepatocytes are long lasting source for treatment of liver injuries and high throughput screening of drugs [20, 23, 24]. Transplantation of the inert biomaterial encapsulated hESCs-derived pancreatic progenitors (CD24+, CD49+, and CD133+) differentiates into -cells, minimizing high fat diet induced glycemic and obesity effects in mice [25] (). Addition of antidiabetic drugs into transdifferentiation regime can boost ESCs conservation into -cells [25], which theoretically can cure T2DM permanently [25]. ESCs can be differentiated directly into insulin secreting -cells (marked with GLUT2, INS1, GCK, and PDX1) which can be achieved through PDX1 mediated epigenetic reprogramming [26]. Globally, osteoarthritis affects millions of people and occurs when cartilage at joints wears away, causing stiffness of the joints. The available therapeutics for arthritis relieve symptoms but do not initiate reverse generation of cartilage. For young individuals and athletes replacement of joints is not feasible like old populations; in that case transplantation of stem cells represents an alternative for healing cartilage injuries [27]. Chondrocytes, the cartilage forming cells derived from hESC, embedded in fibrin gel effectively heal defective cartilage within 12 weeks, when transplanted to focal cartilage defects of knee joints in mice without any negative effect [27]. Transplanted chondrocytes form cell aggregates, positive for SOX9 and collagen II, and defined chondrocytes are active for more than 12wks at transplantation site, advocating clinical suitability of chondrocytes for treatment of cartilage lesions [27]. The integrity of ESCs to integrate and differentiate into electrophysiologically active cells provides a means for natural regulation of heart rhythm as biological pacemaker. Coaxing of ESCs into inert biomaterial as well as propagation in defined culture conditions leads to transdifferentiation of ESCs to become sinoatrial node (SAN) pacemaker cells (PCs) [28]. Genomic incorporation TBox3 into ESCs ex vivo leads to generation of PCs-like cells; those express activated leukocyte cells adhesion molecules (ALCAM) and exhibit similarity to PCs for gene expression and immune functions [28]. Transplantation of PCs can restore pacemaker functions of the ailing heart [28]. In summary, ESCs can be transdifferentiated into any kinds of cells representing three germ layers of the body, being most promising source of regenerative medicine for tissue regeneration and disease therapy (). Ethical concerns limit the applications of ESCs, where set guidelines need to be followed; in that case TSPSCs, MSCs, UCSCs, BMSCs, and iPSCs can be explored as alternatives.

TSPSCs maintain tissue homeostasis through continuous cell division, but, unlike ESCs, TSPSCs retain stem cells plasticity and differentiation in tissue specific manner, giving rise to few types of cells (). The number of TSPSCs population to total cells population is too low; in that case their harvesting as well as in vitro manipulation is really a tricky task [29], to explore them for therapeutic scale. Human body has foundation from various types of TSPSCs; discussing the therapeutic application for all types is not feasible. This section of review discusses therapeutic application of pancreatic progenitor cells (PPCs), dental pulp stem cells (DPSCs), inner ear stem cells (IESCs), intestinal progenitor cells (IPCs), limbal progenitor stem cells (LPSCs), epithelial progenitor stem cells (EPSCs), mesoangioblasts (MABs), spermatogonial stem cells (SSCs), the skin derived precursors (SKPs), and adipose derived stem cells (AdSCs) (; ). During embryogenesis PPCs give rise to insulin-producing -cells. The differentiation of PPCs to become -cells is negatively regulated by insulin [30]. PPCs require active FGF and Notch signalling; growing more rapidly in community than in single cell populations advocates the functional importance of niche effect in self-renewal and transdifferentiation processes. In 3D-scaffold culture system, mice embryo derived PPCs grow into hollow organoid spheres; those finally differentiate into insulin-producing -cell clusters [29]. The DSPSCs, responsible for maintenance of teeth health status, can be sourced from apical papilla, deciduous teeth, dental follicle, and periodontal ligaments, have emerged as regenerative medicine candidate, and might be explored for treatment of various kinds of disease including restoration neurogenic functions in teeth [31, 32]. Expansion of DSPSCs in chemically defined neuronal culture medium transforms them into a mixed population of cholinergic, GABAergic, and glutaminergic neurons; those are known to respond towards acetylcholine, GABA, and glutamine stimulations in vivo. These transformed neuronal cells express nestin, glial fibrillary acidic protein (GFAP), III-tubulin, and voltage gated L-type Ca2+ channels [32]. However, absence of Na+ and K+ channels does not support spontaneous action potential generation, necessary for response generation against environmental stimulus. All together, these primordial neuronal stem cells have possible therapeutic potential for treatment of neurodental problems [32]. Sometimes, brain tumor chemotherapy can cause neurodegeneration mediated cognitive impairment, a condition known as chemobrain [33]. The intrahippocampal transplantation of human derived neuronal stem cells to cyclophosphamide behavioural decremented mice restores cognitive functions in a month time. Here the transplanted stem cells differentiate into neuronal and astroglial lineage, reduce neuroinflammation, and restore microglial functions [33]. Furthermore, transplantation of stem cells, followed by chemotherapy, directs pyramidal and granule-cell neurons of the gyrus and CA1 subfields of hippocampus which leads to reduction in spine and dendritic cell density in the brain. These findings suggest that transplantation of stem cells to cranium restores cognitive functions of the chemobrain [33]. The hair cells of the auditory system produced during development are not postmitotic; loss of hair cells cannot be replaced by inner ear stem cells, due to active state of the Notch signalling [34]. Stimulation of inner ear progenitors with -secretase inhibitor ({"type":"entrez-nucleotide","attrs":{"text":"LY411575","term_id":"1257853995","term_text":"LY411575"}}LY411575) abrogates Notch signalling through activation of transcription factor atonal homologue 1 (Atoh1) and directs transdifferentiation of progenitors into cochlear hair cells [34]. Transplantation of in vitro generated hair cells restores acoustic functions in mice, which can be the potential regenerative medicine candidates for the treatment of deafness [34]. Generation of the hair cells also can be achieved through overexpression of -catenin and Atoh1 in Lrg5+ cells in vivo [35]. Similar to ear progenitors, intestine of the digestive tract also has its own tissue specific progenitor stem cells, mediating regeneration of the intestinal tissue [34, 36]. Dysregulation of the common stem cells signalling pathways, Notch/BMP/TGF-/Wnt, in the intestinal tissue leads to disease. Information on these signalling pathways [37] is critically important in designing therapeutics. Coaxing of the intestinal tissue specific progenitors with immune cells (macrophages), connective tissue cells (myofibroblasts), and probiotic bacteria into 3D-scaffolds of inert biomaterial, crafting biological environment, is suitable for differentiation of progenitors to occupy the crypt-villi structures into these scaffolds [36]. Omental implementation of these crypt-villi structures to dogs enhances intestinal mucosa through regeneration of goblet cells containing intestinal tissue [36]. These intestinal scaffolds are close approach for generation of implantable intestinal tissue, divested by infection, trauma, cancer, necrotizing enterocolitis (NEC), and so forth [36]. In vitro culture conditions cause differentiation of intestinal stem cells to become other types of cells, whereas incorporation of valproic acid and CHIR-99021 in culture conditions avoids differentiation of intestinal stem cells, enabling generation of indefinite pool of stem cells to be used for regenerative applications [38]. The limbal stem cells of the basal limbal epithelium, marked with ABCB5, are essential for regeneration and maintenance of corneal tissue [39]. Functional status of ABCB5 is critical for survival and functional integrity of limbal stem cells, protecting them from apoptotic cell death [39]. Limbal stem cells deficiency leads to replacement of corneal epithelium with visually dead conjunctival tissue, which can be contributed by burns, inflammation, and genetic factors [40]. Transplanted human cornea stem cells to mice regrown into fully functional human cornea, possibly supported by blood eye barrier phenomena, can be used for treatment of eye diseases, where regeneration of corneal tissue is critically required for vision restoration [39]. Muscle degenerative disease like duchenne muscular dystrophy (DMD) can cause extensive thrashing of muscle tissue, where tissue engineering technology can be deployed for functional restoration of tissue through regeneration [41]. Encapsulation of mouse or human derived MABs (engineered to express placental derived growth factor (PDGF)) into polyethylene glycol (PEG) fibrinogen hydrogel and their transplantation beneath the skin at ablated tibialis anterior form artificial muscles, which are functionally similar to those of normal tibialis anterior muscles [41]. The PDGF attracts various cell types of vasculogenic and neurogenic potential to the site of transplantation, supporting transdifferentiation of mesoangioblasts to become muscle fibrils [41]. The therapeutic application of MABs in skeletal muscle regeneration and other therapeutic outcomes has been reviewed by others [42]. One of the most important tissue specific stem cells, the male germline stem cells or spermatogonial stem cells (SSCs), produces spermatogenic lineage through mesenchymal and epithets cells [43] which itself creates niche effect on other cells. In vivo transplantation of SSCs with prostate, skin, and uterine mesenchyme leads to differentiation of these cells to become epithelia of the tissue of origin [43]. These newly formed tissues exhibit all physical and physiological characteristics of prostate and skin and the physical characteristics of prostate, skin, and uterus, express tissue specific markers, and suggest that factors secreted from SSCs lead to lineage conservation which defines the importance of niche effect in regenerative medicine [43]. According to an estimate, more than 100 million people are suffering from the condition of diabetic retinopathy, a progressive dropout of vascularisation in retina that leads to loss of vision [44]. The intravitreal injection of adipose derived stem cells (AdSCs) to the eye restores microvascular capillary bed in mice. The AdSCs from healthy donor produce higher amounts of vasoprotective factors compared to glycemic mice, enabling superior vascularisation [44]. However use of AdSCs for disease therapeutics needs further standardization for cell counts in dose of transplant and monitoring of therapeutic outcomes at population scale [44]. Apart from AdSCs, other kinds of stem cells also have therapeutic potential in regenerative medicine for treatment of eye defects, which has been reviewed by others [45]. Fallopian tubes, connecting ovaries to uterus, are the sites where fertilization of the egg takes place. Infection in fallopian tubes can lead to inflammation, tissue scarring, and closure of the fallopian tube which often leads to infertility and ectopic pregnancies. Fallopian is also the site where onset of ovarian cancer takes place. The studies on origin and etiology of ovarian cancer are restricted due to lack of technical advancement for culture of epithelial cells. The in vitro 3D organoid culture of clinically obtained fallopian tube epithelial cells retains their tissue specificity, keeps cells alive, which differentiate into typical ciliated and secretory cells of fallopian tube, and advocates that ectopic examination of fallopian tube in organoid culture settings might be the ideal approach for screening of cancer [46]. The sustained growth and differentiation of fallopian TSPSCs into fallopian tube organoid depend both on the active state of the Wnt and on paracrine Notch signalling [46]. Similar to fallopian tube stem cells, subcutaneous visceral tissue specific cardiac adipose (CA) derived stem cells (AdSCs) have the potential of differentiation into cardiovascular tissue [47]. Systemic infusion of CA-AdSCs into ischemic myocardium of mice regenerates heart tissue and improves cardiac function through differentiation to endothelial cells, vascular smooth cells, and cardiomyocytes and vascular smooth cells. The differentiation and heart regeneration potential of CA-AdSCs are higher than AdSCs [48], representing CA-AdSCs as potent regenerative medicine candidates for myocardial ischemic therapy [47]. The skin derived precursors (SKPs), the progenitors of dermal papilla/hair/hair sheath, give rise to multiple tissues of mesodermal and/or ectodermal origin such as neurons, Schwann cells, adipocytes, chondrocytes, and vascular smooth muscle cells (VSMCs). VSMCs mediate wound healing and angiogenesis process can be derived from human foreskin progenitor SKPs, suggesting that SKPs derived VSMCs are potential regenerative medicine candidates for wound healing and vasculature injuries treatments [49]. In summary, TSPSCs are potentiated with tissue regeneration, where advancement in organoid culture (; ) technologies defines the importance of niche effect in tissue regeneration and therapeutic outcomes of ex vivo expanded stem cells.

MSCs, the multilineage stem cells, differentiate only to tissue of mesodermal origin, which includes tendons, bone, cartilage, ligaments, muscles, and neurons [50]. MSCs are the cells which express combination of markers: CD73+, CD90+, CD105+, CD11b, CD14, CD19, CD34, CD45, CD79a, and HLA-DR, reviewed elsewhere [50]. The application of MSCs in regenerative medicine can be generalized from ongoing clinical trials, phasing through different state of completions, reviewed elsewhere [90]. This section of review outlines the most recent representative applications of MSCs (; ). The anatomical and physiological characteristics of both donor and receiver have equal impact on therapeutic outcomes. The bone marrow derived MSCs (BMDMSCs) from baboon are morphologically and phenotypically similar to those of bladder stem cells and can be used in regeneration of bladder tissue. The BMDMSCs (CD105+, CD73+, CD34, and CD45), expressing GFP reporter, coaxed with small intestinal submucosa (SIS) scaffolds, augment healing of degenerated bladder tissue within 10wks of the transplantation [51]. The combinatorial CD characterized MACs are functionally active at transplantation site, which suggests that CD characterization of donor MSCs yields superior regenerative outcomes [51]. MSCs also have potential to regenerate liver tissue and treat liver cirrhosis, reviewed elsewhere [91]. The regenerative medicinal application of MSCs utilizes cells in two formats as direct transplantation or first transdifferentiation and then transplantation; ex vivo transdifferentiation of MSCs deploys retroviral delivery system that can cause oncogenic effect on cells. Nonviral, NanoScript technology, comprising utility of transcription factors (TFs) functionalized gold nanoparticles, can target specific regulatory site in the genome effectively and direct differentiation of MSCs into another cell fate, depending on regime of TFs. For example, myogenic regulatory factor containing NanoScript-MRF differentiates the adipose tissue derived MSCs into muscle cells [92]. The multipotency characteristics represent MSCs as promising candidate for obtaining stable tissue constructs through coaxed 3D organoid culture; however heterogeneous distribution of MSCs slows down cell proliferation, rendering therapeutic applications of MSCs. Adopting two-step culture system for MSCs can yield homogeneous distribution of MSCs in biomaterial scaffolds. For example, fetal-MSCs coaxed in biomaterial when cultured first in rotating bioreactor followed with static culture lead to homogeneous distribution of MSCs in ECM components [7]. Occurrence of dental carries, periodontal disease, and tooth injury can impact individual's health, where bioengineering of teeth can be the alternative option. Coaxing of epithelial-MSCs with dental stem cells into synthetic polymer gives rise to mature teeth unit, which consisted of mature teeth and oral tissue, offering multiple regenerative therapeutics, reviewed elsewhere [52]. Like the tooth decay, both human and animals are prone to orthopedic injuries, affecting bones, joint, tendon, muscles, cartilage, and so forth. Although natural healing potential of bone is sufficient to heal the common injuries, severe trauma and tumor-recession can abrogate germinal potential of bone-forming stem cells. In vitro chondrogenic, osteogenic, and adipogenic potential of MSCs advocates therapeutic applications of MSCs in orthopedic injuries [53]. Seeding of MSCs, coaxed into biomaterial scaffolds, at defective bone tissue, regenerates defective bone tissues, within fourwks of transplantation; by the end of 32wks newly formed tissues integrate into old bone [54]. Osteoblasts, the bone-forming cells, have lesser actin cytoskeleton compared to adipocytes and MSCs. Treatment of MSCs with cytochalasin-D causes rapid transportation of G-actin, leading to osteogenic transformation of MSCs. Furthermore, injection of cytochalasin-D to mice tibia also promotes bone formation within a wk time frame [55]. The bone formation processes in mice, dog, and human are fundamentally similar, so outcomes of research on mice and dogs can be directional for regenerative application to human. Injection of MSCs to femur head of Legg-Calve-Perthes suffering dog heals the bone very fast and reduces the injury associated pain [55]. Degeneration of skeletal muscle and muscle cramps are very common to sledge dogs, animals, and individuals involved in adventurous athletics activities. Direct injection of adipose tissue derived MSCs to tear-site of semitendinosus muscle in dogs heals injuries much faster than traditional therapies [56]. Damage effect treatment for heart muscle regeneration is much more complex than regeneration of skeletal muscles, which needs high grade fine-tuned coordination of neurons with muscles. Coaxing of MSCs into alginate gel increases cell retention time that leads to releasing of tissue repairing factors in controlled manner. Transplantation of alginate encapsulated cells to mice heart reduces scar size and increases vascularisation, which leads to restoration of heart functions. Furthermore, transplanted MSCs face host inhospitable inflammatory immune responses and other mechanical forces at transplantation site, where encapsulation of cells keeps them away from all sorts of mechanical forces and enables sensing of host tissue microenvironment, and respond accordingly [57]. Ageing, disease, and medicine consumption can cause hair loss, known as alopecia. Although alopecia has no life threatening effects, emotional catchments can lead to psychological disturbance. The available treatments for alopecia include hair transplantation and use of drugs, where drugs are expensive to afford and generation of new hair follicle is challenging. Dermal papillary cells (DPCs), the specialized MSCs localized in hair follicle, are responsible for morphogenesis of hair follicle and hair cycling. The layer-by-layer coating of DPCs, called GAG coating, consists of coating of geletin as outer layer, middle layer of fibroblast growth factor 2 (FGF2) loaded alginate, and innermost layer of geletin. GAG coating creates tissue microenvironment for DPCs that can sustain immunological and mechanical obstacles, supporting generation of hair follicle. Transplantation of GAG-coated DPCs leads to abundant hair growth and maturation of hair follicle, where GAG coating serves as ECM, enhancing intrinsic therapeutic potential of DPCs [58]. During infection, the inflammatory cytokines secreted from host immune cells attract MSCs to the site of inflammation, which modulates inflammatory responses, representing MSCs as key candidate of regenerative medicine for infectious disease therapeutics. Coculture of macrophages (M) and adipose derived MSCs from Leishmania major (LM) susceptible and resistant mice demonstrates that AD-MSCs educate M against LM infection, differentially inducing M1 and M2 phenotype that represents AD-MSC as therapeutic agent for leishmanial therapy [93]. In summary, the multilineage differentiation potential of MSCs, as well as adoption of next-generation organoid culture system, avails MSCs as ideal regenerative medicine candidate.

Umbilical cord, generally thrown at the time of child birth, is the best known source for stem cells, procured in noninvasive manner, having lesser ethical constraints than ESCs. Umbilical cord is rich source of hematopoietic stem cells (HSCs) and MSCs, which possess enormous regeneration potential [94] (; ). The HSCs of cord blood are responsible for constant renewal of all types of blood cells and protective immune cells. The proliferation of HSCs is regulated by Musashi-2 protein mediated attenuation of Aryl hydrocarbon receptor (AHR) signalling in stem cells [95]. UCSCs can be cryopreserved at stem cells banks (; ), in operation by both private and public sector organization. Public stem cells banks operate on donation formats and perform rigorous screening for HLA typing and donated UCSCs remain available to anyone in need, whereas private stem cell banks operation is more personalized, availing cells according to donor consent. Stem cell banking is not so common, even in developed countries. Survey studies find that educated women are more eager to donate UCSCs, but willingness for donation decreases with subsequent deliveries, due to associated cost and safety concerns for preservation [96]. FDA has approved five HSCs for treatment of blood and other immunological complications [97]. The amniotic fluid, drawn during pregnancy for standard diagnostic purposes, is generally discarded without considering its vasculogenic potential. UCSCs are the best alternatives for those patients who lack donors with fully matched HLA typing for peripheral blood and PBMCs and bone marrow [98]. One major issue with UCSCs is number of cells in transplant, fewer cells in transplant require more time for engraftment to mature, and there are also risks of infection and mortality; in that case ex vivo propagation of UCSCs can meet the demand of desired outcomes. There are diverse protocols, available for ex vivo expansion of UCSCs, reviewed elsewhere [99]. Amniotic fluid stem cells (AFSCs), coaxed to fibrin (required for blood clotting, ECM interactions, wound healing, and angiogenesis) hydrogel and PEG supplemented with vascular endothelial growth factor (VEGF), give rise to vascularised tissue, when grafted to mice, suggesting that organoid cultures of UCSCs have promise for generation of biocompatible tissue patches, for treating infants born with congenital heart defects [59]. Retroviral integration of OCT4, KLF4, cMYC, and SOX2 transforms AFSCs into pluripotency stem cells known as AFiPSCs which can be directed to differentiate into extraembryonic trophoblast by BMP2 and BMP4 stimulation, which can be used for regeneration of placental tissues [60]. Wharton's jelly (WJ), the gelatinous substance inside umbilical cord, is rich in mucopolysaccharides, fibroblast, macrophages, and stem cells. The stem cells from UCB and WJ can be transdifferentiated into -cells. Homogeneous nature of WJ-SCs enables better differentiation into -cells; transplantation of these cells to streptozotocin induced diabetic mice efficiently brings glucose level to normal [7]. Easy access and expansion potential and plasticity to differentiate into multiple cell lineages represent WJ as an ideal candidate for regenerative medicine but cells viability changes with passages with maximum viable population at 5th-6th passages. So it is suggested to perform controlled expansion of WJ-MSCS for desired regenerative outcomes [9]. Study suggests that CD34+ expression leads to the best regenerative outcomes, with less chance of host-versus-graft rejection. In vitro expansion of UCSCs, in presence of StemRegenin-1 (SR-1), conditionally expands CD34+ cells [61]. In type I diabetic mellitus (T1DM), T-cell mediated autoimmune destruction of pancreatic -cells occurs, which has been considered as tough to treat. Transplantation of WJ-SCs to recent onset-T1DM patients restores pancreatic function, suggesting that WJ-MSCs are effective in regeneration of pancreatic tissue anomalies [62]. WJ-MSCs also have therapeutic importance for treatment of T2DM. A non-placebo controlled phase I/II clinical trial demonstrates that intravenous and intrapancreatic endovascular injection of WJ-MSCs to T2DM patients controls fasting glucose and glycated haemoglobin through improvement of -cells functions, evidenced by enhanced c-peptides and reduced inflammatory cytokines (IL-1 and IL-6) and T-cells counts [63]. Like diabetes, systematic lupus erythematosus (SLE) also can be treated with WJ-MSCs transplantation. During progression of SLE host immune system targets its own tissue leading to degeneration of renal, cardiovascular, neuronal, and musculoskeletal tissues. A non-placebo controlled follow-up study on 40 SLE patients demonstrates that intravenous infusion of WJ-MSC improves renal functions and decreases systematic lupus erythematosus disease activity index (SLEDAI) and British Isles Lupus Assessment Group (BILAG), and repeated infusion of WJ-MSCs protects the patient from relapse of the disease [64]. Sometimes, host inflammatory immune responses can be detrimental for HSCs transplantation and blood transfusion procedures. Infusion of WJ-MSC to patients, who had allogenic HSCs transplantation, reduces haemorrhage inflammation (HI) of bladder, suggesting that WJ-MSCs are potential stem cells adjuvant in HSCs transplantation and blood transfusion based therapies [100]. Apart from WJ, umbilical cord perivascular space and cord vein are also rich source for obtaining MSCs. The perivascular MSCs of umbilical cord are more primitive than WJ-MSCs and other MSCs from cord suggest that perivascular MSCs might be used as alternatives for WJ-MSCs for regenerative therapeutics outcome [101]. Based on origin, MSCs exhibit differential in vitro and in vivo properties and advocate functional characterization of MSCs, prior to regenerative applications. Emerging evidence suggests that UCSCs can heal brain injuries, caused by neurodegenerative diseases like Alzheimer's, Krabbe's disease, and so forth. Krabbe's disease, the infantile lysosomal storage disease, occurs due to deficiency of myelin synthesizing enzyme (MSE), affecting brain development and cognitive functions. Progression of neurodegeneration finally leads to death of babies aged two. Investigation shows that healing of peripheral nervous system (PNS) and central nervous system (CNS) tissues with Krabbe's disease can be achieved by allogenic UCSCs. UCSCs transplantation to asymptomatic infants with subsequent monitoring for 46 years reveals that UCSCs recover babies from MSE deficiency, improving myelination and cognitive functions, compared to those of symptomatic babies. The survival rate of transplanted UCSCs in asymptomatic and symptomatic infants was 100% and 43%, respectively, suggesting that early diagnosis and timely treatment are critical for UCSCs acceptance for desired therapeutic outcomes. UCSCs are more primitive than BMSCs, so perfect HLA typing is not critically required, representing UCSCs as an excellent source for treatment of all the diseases involving lysosomal defects, like Krabbe's disease, hurler syndrome, adrenoleukodystrophy (ALD), metachromatic leukodystrophy (MLD), Tay-Sachs disease (TSD), and Sandhoff disease [65]. Brain injuries often lead to cavities formation, which can be treated from neuronal parenchyma, generated ex vivo from UCSCs. Coaxing of UCSCs into human originated biodegradable matrix scaffold and in vitro expansion of cells in defined culture conditions lead to formation of neuronal organoids, within threewks' time frame. These organoids structurally resemble brain tissue and consisted of neuroblasts (GFAP+, Nestin+, and Ki67+) and immature stem cells (OCT4+ and SOX2+). The neuroblasts of these organoids further can be differentiated into mature neurons (MAP2+ and TUJ1+) [66]. Administration of high dose of drugs in divesting neuroblastoma therapeutics requires immediate restoration of hematopoiesis. Although BMSCs had been promising in restoration of hematopoiesis UCSCs are sparely used in clinical settings. A case study demonstrates that neuroblastoma patients who received autologous UCSCs survive without any associated side effects [12]. During radiation therapy of neoplasm, spinal cord myelitis can occur, although occurrence of myelitis is a rare event and usually such neurodegenerative complication of spinal cord occurs 624 years after exposure to radiations. Transplantation of allogenic UC-MSCs in laryngeal patients undergoing radiation therapy restores myelination [102]. For treatment of neurodegenerative disease like Alzheimer's disease (AD), amyotrophic lateral sclerosis (ALS), traumatic brain injuries (TBI), Parkinson's, SCI, stroke, and so forth, distribution of transplanted UCSCs is critical for therapeutic outcomes. In mice and rat, injection of UCSCs and subsequent MRI scanning show that transplanted UCSCs migrate to CNS and multiple peripheral organs [67]. For immunomodulation of tumor cells disease recovery, transplantation of allogenic DCs is required. The CD11c+DCs, derived from UCB, are morphologically and phenotypically similar to those of peripheral blood derived CTLs-DCs, suggesting that UCB-DCs can be used for personalized medicine of cancer patient, in need for DCs transplantation [103]. Coculture of UCSCs with radiation exposed human lung fibroblast stops their transdifferentiation, which suggests that factors secreted from UCSCs may restore niche identity of fibroblast, if they are transplanted to lung after radiation therapy [104]. Tearing of shoulder cuff tendon can cause severe pain and functional disability, whereas ultrasound guided transplantation of UCB-MSCs in rabbit regenerates subscapularis tendon in fourwks' time frame, suggesting that UCB-MSCs are effective enough to treat tendons injuries when injected to focal points of tear-site [68]. Furthermore, transplantation of UCB-MSCs to chondral cartilage injuries site in pig knee along with HA hydrogel composite regenerates hyaline cartilage [69], suggesting that UCB-MSCs are effective regenerative medicine candidate for treating cartilage and ligament injuries. Physiologically circulatory systems of brain, placenta, and lungs are similar. Infusion of UCB-MSCs to preeclampsia (PE) induced hypertension mice reduces the endotoxic effect, suggesting that UC-MSCs are potential source for treatment of endotoxin induced hypertension during pregnancy, drug abuse, and other kinds of inflammatory shocks [105]. Transplantation of UCSCs to severe congenital neutropenia (SCN) patients restores neutrophils count from donor cells without any side effect, representing UCSCs as potential alternative for SCN therapy, when HLA matched bone marrow donors are not accessible [106]. In clinical settings, the success of myocardial infarction (MI) treatment depends on ageing, systemic inflammation in host, and processing of cells for infusion. Infusion of human hyaluronan hydrogel coaxed UCSCs in pigs induces angiogenesis, decreases scar area, improves cardiac function at preclinical level, and suggests that the same strategy might be effective for human [107]. In stem cells therapeutics, UCSCs transplantation can be either autologous or allogenic. Sometimes, the autologous UCSCs transplants cannot combat over tumor relapse, observed in Hodgkin's lymphoma (HL), which might require second dose transplantation of allogenic stem cells, but efficacy and tolerance of stem cells transplant need to be addressed, where tumor replace occurs. A case study demonstrates that second dose allogenic transplants of UCSCs effective for HL patients, who had heavy dose in prior transplant, increase the long term survival chances by 30% [10]. Patients undergoing long term peritoneal renal dialysis are prone to peritoneal fibrosis and can change peritoneal structure and failure of ultrafiltration processes. The intraperitoneal (IP) injection of WJ-MSCs prevents methylglyoxal induced programmed cell death and peritoneal wall thickening and fibrosis, suggesting that WJ-MSCs are effective in therapeutics of encapsulating peritoneal fibrosis [70]. In summary, UCB-HSCs, WJ-MSCs, perivascular MSCs, and UCB-MSCs have tissue regeneration potential.

Bone marrow found in soft spongy bones is responsible for formation of all peripheral blood and comprises hematopoietic stem cells (producing blood cells) and stromal cells (producing fat, cartilage, and bones) [108] (; ). Visually bone marrow has two types, red marrow (myeloid tissue; producing RBC, platelets, and most of WBC) and yellow marrow (producing fat cells and some WBC) [108]. Imbalance in marrow composition can culminate to the diseased condition. Since 1980, bone marrow transplantation is widely accepted for cancer therapeutics [109]. In order to avoid graft rejection, HLA typing of donors is a must, but completely matched donors are limited to family members, which hampers allogenic transplantation applications. Since matching of all HLA antigens is not critically required, in that case defining the critical antigens for haploidentical allogenic donor for patients, who cannot find fully matched donor, might relieve from donor constraints. Two-step administration of lymphoid and myeloid BMSCs from haploidentical donor to the patients of aplastic anaemia and haematological malignancies reconstructs host immune system and the outcomes are almost similar to fully matched transplants, which recommends that profiling of critically important HLA is sufficient for successful outcomes of BMSCs transplantation. Haploidentical HLA matching protocol is the major process for minorities and others who do not have access to matched donor [71]. Furthermore, antigen profiling is not the sole concern for BMSCs based therapeutics. For example, restriction of HIV1 (human immune deficiency virus) infection is not feasible through BMSCs transplantation because HIV1 infection is mediated through CD4+ receptors, chemokine CXC motif receptor 4 (CXCR4), and chemokine receptor 5 (CCR5) for infecting and propagating into T helper (Th), monocytes, macrophages, and dendritic cells (DCs). Genetic variation in CCR2 and CCR5 receptors is also a contributory factor; mediating protection against infection has been reviewed elsewhere [110]. Engineering of hematopoietic stem and progenitor cells (HSPCs) derived CD4+ cells to express HIV1 antagonistic RNA, specifically designed for targeting HIV1 genome, can restrict HIV1 infection, through immune elimination of latently infected CD4+ cells. A single dose infusion of genetically modified (GM), HIV1 resistant HSPCs can be the alternative of HIV1 retroviral therapy. In the present scenario stem cells source, patient selection, transplantation-conditioning regimen, and postinfusion follow-up studies are the major factors, which can limit application of HIV1 resistant GM-HSPCs (CD4+) cells application in AIDS therapy [72, 73]. Platelets, essential for blood clotting, are formed from megakaryocytes inside the bone marrow [74]. Due to infection, trauma, and cancer, there are chances of bone marrow failure. To an extent, spongy bone marrow microenvironment responsible for lineage commitment can be reconstructed ex vivo [75]. The ex vivo constructed 3D-scaffolds consisted of microtubule and silk sponge, flooded with chemically defined organ culture medium, which mimics bone marrow environment. The coculture of megakaryocytes and embryonic stem cells (ESCs) in this microenvironment leads to generation of functional platelets from megakaryocytes [75]. The ex vivo 3D-scaffolds of bone microenvironment can stride the path for generation of platelets in therapeutic quantities for regenerative medication of burns [75] and blood clotting associated defects. Accidents, traumatic injuries, and brain stroke can deplete neuronal stem cells (NSCs), responsible for generation of neurons, astrocytes, and oligodendrocytes. Brain does not repopulate NSCs and heal traumatic injuries itself and transplantation of BMSCs also can heal neurodegeneration alone. Lipoic acid (LA), a known pharmacological antioxidant compound used in treatment of diabetic and multiple sclerosis neuropathy when combined with BMSCs, induces neovascularisation at focal cerebral injuries, within 8wks of transplantation. Vascularisation further attracts microglia and induces their colonization into scaffold, which leads to differentiation of BMSCs to become brain tissue, within 16wks of transplantation. In this approach, healing of tissue directly depends on number of BMSCs in transplantation dose [76]. Dental caries and periodontal disease are common craniofacial disease, often requiring jaw bone reconstruction after removal of the teeth. Traditional therapy focuses on functional and structural restoration of oral tissue, bone, and teeth rather than biological restoration, but BMSCs based therapies promise for regeneration of craniofacial bone defects, enabling replacement of missing teeth in restored bones with dental implants. Bone marrow derived CD14+ and CD90+ stem and progenitor cells, termed as tissue repair cells (TRC), accelerate alveolar bone regeneration and reconstruction of jaw bone when transplanted in damaged craniofacial tissue, earlier to oral implants. Hence, TRC therapy reduces the need of secondary bone grafts, best suited for severe defects in oral bone, skin, and gum, resulting from trauma, disease, or birth defects [77]. Overall, HSCs have great value in regenerative medicine, where stem cells transplantation strategies explore importance of niche in tissue regeneration. Prior to transplantation of BMSCs, clearance of original niche from target tissue is necessary for generation of organoid and organs without host-versus-graft rejection events. Some genetic defects can lead to disorganization of niche, leading to developmental errors. Complementation with human blastocyst derived primary cells can restore niche function of pancreas in pigs and rats, which defines the concept for generation of clinical grade human pancreas in mice and pigs [111]. Similar to other organs, diaphragm also has its own niche. Congenital defects in diaphragm can affect diaphragm functions. In the present scenario functional restoration of congenital diaphragm defects by surgical repair has risk of reoccurrence of defects or incomplete restoration [8]. Decellularization of donor derived diaphragm offers a way for reconstruction of new and functionally compatible diaphragm through niche modulation. Tissue engineering technology based decellularization of diaphragm and simultaneous perfusion of bone marrow mesenchymal stem cells (BM-MSCs) facilitates regeneration of functional scaffolds of diaphragm tissues [8]. In vivo replacement of hemidiaphragm in rats with reseeded scaffolds possesses similar myography and spirometry as it has in vivo in donor rats. These scaffolds retaining natural architecture are devoid of immune cells, retaining intact extracellular matrix that supports adhesion, proliferation, and differentiation of seeded cells [8]. These findings suggest that cadaver obtained diaphragm, seeded with BM-MSCs, can be used for curing patients in need for restoration of diaphragm functions (; ). However, BMSCs are heterogeneous population, which might result in differential outcomes in clinical settings; however clonal expansion of BMSCs yields homogenous cells population for therapeutic application [8]. One study also finds that intracavernous delivery of single clone BMSCs can restore erectile function in diabetic mice [112] and the same strategy might be explored for adult human individuals. The infection of hepatitis C virus (HCV) can cause liver cirrhosis and degeneration of hepatic tissue. The intraparenchymal transplantation of bone marrow mononuclear cells (BMMNCs) into liver tissue decreases aspartate aminotransferase (AST), alanine transaminase (ALT), bilirubin, CD34, and -SMA, suggesting that transplanted BMSCs restore hepatic functions through regeneration of hepatic tissues [113]. In order to meet the growing demand for stem cells transplantation therapy, donor encouragement is always required [8]. The stem cells donation procedure is very simple; with consent donor gets an injection of granulocyte-colony stimulating factor (G-CSF) that increases BMSCs population. Bone marrow collection is done from hip bone using syringe in 4-5hrs, requiring local anaesthesia and within a wk time frame donor gets recovered donation associated weakness.

The field of iPSCs technology and research is new to all other stem cells research, emerging in 2006 when, for the first time, Takahashi and Yamanaka generated ESCs-like cells through genetic incorporation of four factors, Sox2, Oct3/4, Klf4, and c-Myc, into skin fibroblast [3]. Due to extensive nuclear reprogramming, generated iPSCs are indistinguishable from ESCs, for their transcriptome profiling, epigenetic markings, and functional competence [3], but use of retrovirus in transdifferentiation approach has questioned iPSCs technology. Technological advancement has enabled generation of iPSCs from various kinds of adult cells phasing through ESCs or direct transdifferentiation. This section of review outlines most recent advancement in iPSC technology and regenerative applications (; ). Using the new edge of iPSCs technology, terminally differentiated skin cells directly can be transformed into kidney organoids [114], which are functionally and structurally similar to those of kidney tissue in vivo. Up to certain extent kidneys heal themselves; however natural regeneration potential cannot meet healing for severe injuries. During kidneys healing process, a progenitor stem cell needs to become 20 types of cells, required for waste excretion, pH regulation, and restoration of water and electrolytic ions. The procedure for generation of kidney organoids ex vivo, containing functional nephrons, has been identified for human. These ex vivo kidney organoids are similar to fetal first-trimester kidneys for their structure and physiology. Such kidney organoids can serve as model for nephrotoxicity screening of drugs, disease modelling, and organ transplantation. However generation of fully functional kidneys is a far seen event with today's scientific technologies [114]. Loss of neurons in age-related macular degeneration (ARMD) is the common cause of blindness. At preclinical level, transplantation of iPSCs derived neuronal progenitor cells (NPCs) in rat limits progression of disease through generation of 5-6 layers of photoreceptor nuclei, restoring visual acuity [78]. The various approaches of iPSCs mediated retinal regeneration including ARMD have been reviewed elsewhere [79]. Placenta, the cordial connection between mother and developing fetus, gets degenerated in certain pathophysiological conditions. Nuclear programming of OCT4 knock-out (KO) and wild type (WT) mice fibroblast through transient expression of GATA3, EOMES, TFAP2C, and +/ cMYC generates transgene independent trophoblast stem-like cells (iTSCs), which are highly similar to blastocyst derived TSCs for DNA methylation, H3K7ac, nucleosome deposition of H2A.X, and other epigenetic markings. Chimeric differentiation of iTSCs specifically gives rise to haemorrhagic lineages and placental tissue, bypassing pluripotency phase, opening an avenue for generation of fully functional placenta for human [115]. Neurodegenerative disease like Alzheimer's and obstinate epilepsies can degenerate cerebrum, controlling excitatory and inhibitory signals of the brain. The inhibitory tones in cerebral cortex and hippocampus are accounted by -amino butyric acid secreting (GABAergic) interneurons (INs). Loss of these neurons often leads to progressive neurodegeneration. Genomic integration of Ascl1, Dlx5, Foxg1, and Lhx6 to mice and human fibroblast transforms these adult cells into GABAergic-INs (iGABA-INs). These cells have molecular signature of telencephalic INs, release GABA, and show inhibition to host granule neuronal activity [81]. Transplantation of these INs in developing embryo cures from genetic and acquired seizures, where transplanted cells disperse and mature into functional neuronal circuits as local INs [82]. Dorsomorphin and SB-431542 mediated inhibition of TGF- and BMP signalling direct transformation of human iPSCs into cortical spheroids. These cortical spheroids consisted of both peripheral and cortical neurons, surrounded by astrocytes, displaying transcription profiling and electrophysiology similarity with developing fetal brain and mature neurons, respectively [83]. The underlying complex biology and lack of clear etiology and genetic reprogramming and difficulty in recapitulation of brain development have barred understanding of pathophysiology of autism spectrum disorder (ASD) and schizophrenia. 3D organoid cultures of ASD patient derived iPSC generate miniature brain organoid, resembling fetal brain few months after gestation. The idiopathic conditions of these organoids are similar with brain of ASD patients; both possess higher inhibitory GABAergic neurons with imbalanced neuronal connection. Furthermore these organoids express forkhead Box G1 (FOXG1) much higher than normal brain tissue, which explains that FOXG1 might be the leading cause of ASD [84]. Degeneration of other organs and tissues also has been reported, like degeneration of lungs which might occur due to tuberculosis infection, fibrosis, and cancer. The underlying etiology for lung degeneration can be explained through organoid culture. Coaxing of iPSC into inert biomaterial and defined culture leads to formation of lung organoids that consisted of epithelial and mesenchymal cells, which can survive in culture for months. These organoids are miniature lung, resemble tissues of large airways and alveoli, and can be used for lung developmental studies and screening of antituberculosis and anticancer drugs [87]. The conventional multistep reprogramming for iPSCs consumes months of time, while CRISPER-Cas9 system based episomal reprogramming system that combines two steps together enables generation of ESCs-like cells in less than twowks, reducing the chances of culture associated genetic abrasions and unwanted epigenetic [80]. This approach can yield single step ESCs-like cells in more personalized way from adults with retinal degradation and infants with severe immunodeficiency, involving correction for genetic mutation of OCT4 and DNMT3B [80]. The iPSCs expressing anti-CCR5-RNA, which can be differentiated into HIV1 resistant macrophages, have applications in AIDS therapeutics [88]. The diversified immunotherapeutic application of iPSCs has been reviewed elsewhere [89]. The -1 antitrypsin deficiency (A1AD) encoded by serpin peptidase inhibitor clade A member 1 (SERPINA1) protein synthesized in liver protects lungs from neutrophils elastase, the enzyme causing disruption of lungs connective tissue. A1AD deficiency is common cause of both lung and liver disease like chronic obstructive pulmonary disease (COPD) and liver cirrhosis. Patient specific iPSCs from lung and liver cells might explain pathophysiology of A1AD deficiency. COPD patient derived iPSCs show sensitivity to toxic drugs which explains that actual patient might be sensitive in similar fashion. It is known that A1AD deficiency is caused by single base pair mutation and correction of this mutation fixes the A1AD deficiency in hepatic-iPSCs [85]. The high order brain functions, like emotions, anxiety, sleep, depression, appetite, breathing heartbeats, and so forth, are regulated by serotonin neurons. Generation of serotonin neurons occurs prior to birth, which are postmitotic in their nature. Any sort of developmental defect and degeneration of serotonin neurons might lead to neuronal disorders like bipolar disorder, depression, and schizophrenia-like psychiatric conditions. Manipulation of Wnt signalling in human iPSCs in defined culture conditions leads to an in vitro differentiation of iPSCs to serotonin-like neurons. These iPSCs-neurons primarily localize to rhombomere 2-3 segment of rostral raphe nucleus, exhibit electrophysiological properties similar to serotonin neurons, express hydroxylase 2, the developmental marker, and release serotonin in dose and time dependent manner. Transplantation of these neurons might cure from schizophrenia, bipolar disorder, and other neuropathological conditions [116]. The iPSCs technology mediated somatic cell reprogramming of ventricular monocytes results in generation of cells, similar in morphology and functionality with PCs. SA note transplantation of PCs to large animals improves rhythmic heart functions. Pacemaker needs very reliable and robust performance so understanding of transformation process and site of transplantation are the critical aspect for therapeutic validation of iPSCs derived PCs [28]. Diabetes is a major health concern in modern world, and generation of -cells from adult tissue is challenging. Direct reprogramming of skin cells into pancreatic cells, bypassing pluripotency phase, can yield clinical grade -cells. This reprogramming strategy involves transformation of skin cells into definitive endodermal progenitors (cDE) and foregut like progenitor cells (cPF) intermediates and subsequent in vitro expansion of these intermediates to become pancreatic -cells (cPB). The first step is chemically complex and can be understood as nonepisomal reprogramming on day one with pluripotency factors (OCT4, SOX2, KLF4, and hair pin RNA against p53), then supplementation with GFs and chemical supplements on day seven (EGF, bFGF, CHIR, NECA, NaB, Par, and RG), and two weeks later (Activin-A, CHIR, NECA, NaB, and RG) yielding DE and cPF [86]. Transplantation of cPB yields into glucose stimulated secretion of insulin in diabetic mice defines that such cells can be explored for treatment of T1DM and T2DM in more personalized manner [86]. iPSCs represent underrated opportunities for drug industries and clinical research laboratories for development of therapeutics, but safety concerns might limit transplantation applications (; ) [117]. Transplantation of human iPSCs into mice gastrula leads to colonization and differentiation of cells into three germ layers, evidenced with clinical developmental fat measurements. The acceptance of human iPSCs by mice gastrula suggests that correct timing and appropriate reprogramming regime might delimit human mice species barrier. Using this fact of species barrier, generation of human organs in closely associated primates might be possible, which can be used for treatment of genetic factors governed disease at embryo level itself [118]. In summary, iPSCs are safe and effective for treatment of regenerative medicine.

The unstable growth of human population threatens the existence of wildlife, through overexploitation of natural habitats and illegal killing of wild animals, leading many species to face the fate of being endangered and go for extinction. For wildlife conservation, the concept of creation of frozen zoo involves preservation of gene pool and germ plasm from threatened and endangered species (). The frozen zoo tissue samples collection from dead or live animal can be DNA, sperms, eggs, embryos, gonads, skin, or any other tissue of the body [119]. Preserved tissue can be reprogrammed or transdifferentiated to become other types of tissues and cells, which opens an avenue for conservation of endangered species and resurrection of life (). The gonadal tissue from young individuals harbouring immature tissue can be matured in vivo and ex vivo for generation of functional gametes. Transplantation of SSCs to testis of male from the same different species can give rise to spermatozoa of donor cells [120], which might be used for IVF based captive breeding of wild animals. The most dangerous fact in wildlife conservation is low genetic diversity, too few reproductively capable animals which cannot maintain adequate genetic diversity in wild or captivity. Using the edge of iPSC technology, pluripotent stem cells can be generated from skin cells. For endangered drill, Mandrillus leucophaeus, and nearly extinct white rhinoceros, Ceratotherium simum cottoni, iPSC has been generated in 2011 [121]. The endangered animal drill (Mandrillus leucophaeus) is genetically very close to human and often suffers from diabetes, while rhinos are genetically far removed from other primates. The progress in iPSCs, from the human point of view, might be transformed for animal research for recapturing reproductive potential and health in wild animals. However, stem cells based interventions in wild animals are much more complex than classical conservation planning and biomedical research has to face. Conversion of iPSC into egg or sperm can open the door for generation of IVF based embryo; those might be transplanted in womb of live counterparts for propagation of population. Recently, iPSCs have been generated for snow leopard (Panthera uncia), native to mountain ranges of central Asia, which belongs to cat family; this breakthrough has raised the possibilities for cryopreservation of genetic material for future cloning and other assisted reproductive technology (ART) applications, for the conservation of cat species and biodiversity. Generation of leopard iPSCs has been achieved through retroviral-system based genomic integration of OCT4, SOX2, KLF4, cMYC, and NANOG. These iPSCs from snow leopard also open an avenue for further transformation of iPSCs into gametes [122]. The in vivo maturation of grafted tissue depends both on age and on hormonal status of donor tissue. These facts are equally applicable to accepting host. Ectopic xenografts of cryopreserved testis tissue from Indian spotted deer (Moschiola indica) to nude mice yielded generation of spermatocytes [123], suggesting that one-day procurement of functional sperm from premature tissue might become a general technique in wildlife conservation. In summary, tissue biopsies from dead or live animals can be used for generation of iPSCs and functional gametes; those can be used in assisted reproductive technology (ART) for wildlife conservation.

The spectacular progress in the field of stem cells research represents great scope of stem cells regenerative therapeutics. It can be estimated that by 2020 or so we will be able to produce wide array of tissue, organoid, and organs from adult stem cells. Inductions of pluripotency phenotypes in terminally differentiated adult cells have better therapeutic future than ESCs, due to least ethical constraints with adult cells. In the coming future, there might be new pharmaceutical compounds; those can activate tissue specific stem cells, promote stem cells to migrate to the side of tissue injury, and promote their differentiation to tissue specific cells. Except few countries, the ongoing financial and ethical hindrance on ESCs application in regenerative medicine have more chance for funding agencies to distribute funding for the least risky projects on UCSCs, BMSCs, and TSPSCs from biopsies. The existing stem cells therapeutics advancements are more experimental and high in cost; due to that application on broad scale is not feasible in current scenario. In the near future, the advancements of medical science presume using stem cells to treat cancer, muscles damage, autoimmune disease, and spinal cord injuries among a number of impairments and diseases. It is expected that stem cells therapies will bring considerable benefits to the patients suffering from wide range of injuries and disease. There is high optimism for use of BMSCs, TSPSCs, and iPSCs for treatment of various diseases to overcome the contradictions associated with ESCs. For advancement of translational application of stem cells, there is a need of clinical trials, which needs funding rejoinder from both public and private organizations. The critical evaluation of regulatory guidelines at each phase of clinical trial is a must to comprehend the success and efficacy in time frame.

Dr. Anuradha Reddy from Centre for Cellular and Molecular Biology Hyderabad and Mrs. Sarita Kumari from Department of Yoga Science, BU, Bhopal, India, are acknowledged for their critical suggestions and comments on paper.

There are no competing interests associated with this paper.

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Regenerative & Sports Medicine | Dr. Rand McClain

Sunday, November 7th, 2021

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AMSSM Releases Position Statement on Regenerative Medicine in Sports Medicine – Newswise

Sunday, November 7th, 2021

Newswise The American Medical Society for Sports Medicine (AMSSM) has released a position statement on Principles for the Responsible Use of Regenerative Medicine in Sports Medicine.

This position statement provides sports medicine physicians with information on regenerative medicine terminology, a brief review of the basic science and clinical studies, regulatory considerations, and best practices for introducing the orthobiologic classification of regenerative therapies into their clinical practice.

The document is being published in the Clinical Journal of Sport Medicine, with accompanying editorial highlights published in the British Journal of Sports Medicine. Both are freely accessible on their respective websites.

Sports medicine physicians would benefit from decision-making guidance about whether to introduce orthobiologics into their practice and how to do it responsibly, said Dr. Jonathan Finnoff, the Chief Medical Officer of the United States Olympic and Paralympic Committee and the lead author of the statement. The information within this statement will help sports medicine physicians make informed and responsible decisions about the role of regenerative medicine and orthobiologics in their practice.

In 2019, the AMSSM Board of Directors established a Regenerative Medicine Task Force, with a subgroup charged to develop a regenerative medicine position statement. The Task Force brought together a writing group that included sports medicine physicians and scientists who are recognized leaders in bioethics, research, and regenerative medicine clinical applications to produce this statement.

The field of regenerative medicine, and the sub-classification of orthobiologics, involves a variety of therapies and techniques focused on the repair or replacement of damaged or diseased tissue to restore function. Despite these novel therapies being very attractive to sports medicine physicians and patients alike, this is a complex and controversial topic.

Common orthobiologics that are employed in research and medical practice are being combined under the umbrella of stem cell therapy in a manner that is confusing to both patients and the public, said Dr. Shane Shapiro, one of the lead authors of the statement. The need for scientifically validated treatments for non-healing orthopedic and sports conditions has increased interest in orthobiologics and other regenerative therapies to address existing treatment gaps.

The document contains brief discussions of the basic science, proposed therapeutic mechanisms of action, and clinical evidence related to regenerative medicine products, including uses for platelet-rich plasma and other cellular therapies. Additionally, the statement features sections regarding regulatory considerations and an in-depth portion on introducing regenerative medicine into clinical practice.

Ultimately, this AMSSM position statement on regenerative medicine advocates for the advancement of orthobiologic science, patient safety and education towards the responsible translation of regenerative therapies, said Dr. Kenneth Mautner, co-lead author of the position statement and an AMSSM Board member.

About the AMSSM: AMSSM is a multi-disciplinary organization of sports medicine physicians dedicated to education, research, advocacy and the care of athletes of all ages. The majority of AMSSM members are primary care physicians with fellowship training and added qualification in sports medicine who then combine their practice of sports medicine with their primary specialty. AMSSM includes members who specialize solely in non-surgical sports medicine and serve as team physicians at the youth level, NCAA, NFL, MLB, NBA, WNBA, MLS and NHL, as well as with Olympic and Paralympic teams. By nature of their training and experience, sports medicine physicians are ideally suited to provide comprehensive medical care for athletes, sports teams or active individuals who are simply looking to maintain a healthy lifestyle. http://www.amssm.org

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AMSSM Releases Position Statement on Regenerative Medicine in Sports Medicine - Newswise

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CRISPR Therapeutics Provides Business Update and Reports Third Quarter 2021 Financial Results – Yahoo Finance

Sunday, November 7th, 2021

-Achieved target enrollment in CTX001 clinical trials for beta thalassemia (TDT) and sickle cell disease (SCD); regulatory submissions planned for late 2022-

-Reported positive results from the ongoing Phase 1 CARBON clinical trial evaluating the safety and efficacy of CTX110 for CD19+ B-cell malignancies; enrollment continues, with potential registrational trial incorporating consolidation dosing expected to initiate in Q1 2022-

-Implementing consolidation dosing protocols for CTX120 and CTX130 clinical trials; enrollment continues, with top-line data expected to report in 1H 2022-

-Regenerative medicine and in vivo programs continue to progress and remain on track-

ZUG, Switzerland and CAMBRIDGE, Mass., Nov. 03, 2021 (GLOBE NEWSWIRE) -- CRISPR Therapeutics (Nasdaq: CRSP), a biopharmaceutical company focused on creating transformative gene-based medicines for serious diseases, today reported financial results for the third quarter ended September 30, 2021.

The third quarter marked significant progress across our portfolio, said Samarth Kulkarni, Ph.D., Chief Executive Officer of CRISPR Therapeutics. With our partner Vertex, we achieved target enrollment for the CTX001 clinical trials in patients with beta thalassemia and sickle cell disease, which can support regulatory submissions in late 2022. Additionally, we demonstrated proof of concept for our allogeneic CAR-T platform with positive data from our CARBON trial of CTX110, which showed that immediately available off-the-shelf cell therapies can offer efficacy similar to autologous CAR-T with a differentiated safety profile for patients with large B-cell lymphomas. Based on these encouraging results, we plan to expand the CARBON trial into a potentially registrational trial in the first quarter of 2022. Furthermore, we hope to bring these transformative allogeneic CAR-T therapies to patients in outpatient and community oncology settings, enabling broad access."

Story continues

Recent Highlights and Outlook

Third Quarter 2021 Financial Results

Cash Position: Cash, cash equivalents and marketable securities were $2,477.4 million as of September 30, 2021, compared to $2,589.4 million as of June 30, 2021. The decrease in cash of $112.0 million was primarily driven by cash used in operating activities to support ongoing research and development of the Companys clinical and pre-clinical programs.

Revenue: Total collaboration revenue was $0.3 million for the third quarter of 2021, compared to $0.1 million for the third quarter of 2020. Collaboration revenue primarily consisted of revenue recognized in connection with our collaboration agreements with Vertex.

R&D Expenses: R&D expenses were $105.3 million for the third quarter of 2021, compared to $71.0 million for the third quarter of 2020. The increase in expense was driven by development activities supporting the advancement of the hemoglobinopathies program and wholly-owned immuno-oncology programs, as well as increased headcount and supporting facilities related expenses.

G&A Expenses: General and administrative expenses were $24.4 million for the third quarter of 2021, compared to $21.5 million for the third quarter of 2020. The increase in general and administrative expenses for the year was primarily driven by headcount-related expense.

Net Loss: Net loss was $127.2 million for the third quarter of 2021, compared to a net loss of $92.4 million for the third quarter of 2020.

About CTX001CTX001 is an investigational, autologous, ex vivo CRISPR/Cas9 gene-edited therapy that is being evaluated for patients suffering from TDT or severe SCD, in which a patients hematopoietic stem cells are edited to produce high levels of fetal hemoglobin (HbF; hemoglobin F) in red blood cells. HbF is a form of the oxygen-carrying hemoglobin that is naturally present at birth, which then switches to the adult form of hemoglobin. The elevation of HbF by CTX001 has the potential to alleviate or eliminate transfusion requirements for patients with TDT and reduce or eliminate painful and debilitating sickle crises for patients with SCD. Earlier results from these ongoing trials were published as a Brief Report in The New England Journal of Medicine in January of 2021.

Based on progress in this program to date, CTX001 has been granted Regenerative Medicine Advanced Therapy (RMAT), Fast Track, Orphan Drug, and Rare Pediatric Disease designations from the U.S. Food and Drug Administration (FDA) for both TDT and SCD. CTX001 has also been granted Orphan Drug Designation from the European Commission, as well as Priority Medicines (PRIME) designation from the European Medicines Agency (EMA), for both TDT and SCD.

Among gene-editing approaches being investigated/evaluated for TDT and SCD, CTX001 is the furthest advanced in clinical development.

About the CRISPR-Vertex CollaborationVertex and CRISPR Therapeutics entered into a strategic research collaboration in 2015 focused on the use of CRISPR/Cas9 to discover and develop potential new treatments aimed at the underlying genetic causes of human disease. CTX001 represents the first potential treatment to emerge from the joint research program. Under a recently amended collaboration agreement, Vertex will lead global development, manufacturing and commercialization of CTX001 and split program costs and profits worldwide 60/40 with CRISPR Therapeutics.

About CLIMB-111The ongoing Phase 1/2 open-label trial, CLIMB-Thal-111, is designed to assess the safety and efficacy of a single dose of CTX001 in patients ages 12 to 35 with TDT. The trial will enroll up to 45 patients and follow patients for approximately two years after infusion. Each patient will be asked to participate in a long-term follow-up trial.

About CLIMB-121The ongoing Phase 1/2 open-label trial, CLIMB-SCD-121, is designed to assess the safety and efficacy of a single dose of CTX001 in patients ages 12 to 35 with severe SCD. The trial will enroll up to 45 patients and follow patients for approximately two years after infusion. Each patient will be asked to participate in a long-term follow-up trial.

About CLIMB-131This is a long-term, open-label trial to evaluate the safety and efficacy of CTX001 in patients who received CTX001 in CLIMB-111 or CLIMB-121. The trial is designed to follow participants for up to 15 years after CTX001 infusion.

About CTX110CTX110, a wholly owned program of CRISPR Therapeutics, is a healthy donor-derived gene-edited allogeneic CAR-T investigational therapy targeting cluster of differentiation 19, or CD19. CTX110 is being investigated in the ongoing CARBON trial.

About CARBONThe ongoing Phase 1 single-arm, multi-center, open label clinical trial, CARBON, is designed to assess the safety and efficacy of several dose levels of CTX110 for the treatment of relapsed or refractory B-cell malignancies.

About CTX120CTX120, a wholly-owned program of CRISPR Therapeutics, is a healthy donor-derived gene-edited allogeneic CAR-T investigational therapy targeting B-cell maturation antigen, or BCMA. CTX120 is being investigated in an ongoing Phase 1 single-arm, multi-center, open-label clinical trial designed to assess the safety and efficacy of several dose levels of CTX120 for the treatment of relapsed or refractory multiple myeloma. CTX120 has been granted Orphan Drug designation from the FDA.

About CTX130CTX130, a wholly-owned program of CRISPR Therapeutics, is a healthy donor-derived gene-edited allogeneic CAR-T investigational therapy targeting cluster of differentiation 70, or CD70, an antigen expressed on various solid tumors and hematologic malignancies. CTX130 is being developed for the treatment of both solid tumors, such as renal cell carcinoma, and T-cell and B-cell hematologic malignancies. CTX130 is being investigated in two ongoing independent Phase 1, single-arm, multi-center, open-label clinical trials that are designed to assess the safety and efficacy of several dose levels of CTX130 for the treatment of relapsed or refractory renal cell carcinoma and various subtypes of lymphoma, respectively.

About CRISPR TherapeuticsCRISPR Therapeutics is a leading gene editing company focused on developing transformative gene-based medicines for serious diseases using its proprietary CRISPR/Cas9 platform. CRISPR/Cas9 is a revolutionary gene editing technology that allows for precise, directed changes to genomic DNA. CRISPR Therapeutics has established a portfolio of therapeutic programs across a broad range of disease areas including hemoglobinopathies, oncology, regenerative medicine and rare diseases. To accelerate and expand its efforts, CRISPR Therapeutics has established strategic collaborations with leading companies including Bayer, Vertex Pharmaceuticals and ViaCyte, Inc. CRISPR Therapeutics AG is headquartered in Zug, Switzerland, with its wholly-owned U.S. subsidiary, CRISPR Therapeutics, Inc., and R&D operations based in Cambridge, Massachusetts, and business offices in San Francisco, California and London, United Kingdom. For more information, please visit http://www.crisprtx.com.

CRISPR THERAPEUTICS word mark and design logo, CTX001, CTX110, CTX120, and CTX130 are trademarks and registered trademarks of CRISPR Therapeutics AG. All other trademarks and registered trademarks are the property of their respective owners.

CRISPR Therapeutics Forward-Looking StatementThis press release may contain a number of forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995, as amended, including statements made by Dr. Kulkarni in this press release, as well as statements regarding CRISPR Therapeutics expectations about any or all of the following: (i) the safety, efficacy, data and clinical progress of CRISPR Therapeutics various clinical programs, including CTX001, CTX110, CTX120 and CTX130; (ii) the status of clinical trials and preclinical studies (including, without limitation, the expected timing of data releases and development, as well as initiation and completion of clinical trials) and development timelines for CRISPR Therapeutics product candidates; (iii) expectations regarding the data that has been presented from our various clinical trials (including our CARBON trial) as well as data that will be generated by ongoing and planned clinical trials, and the ability to use that data for the design and initiation of further clinical trials or to support regulatory filings; (iv) the actual or potential benefits of regulatory designations; (v) the potential benefits of CRISPR Therapeutics collaborations and strategic partnerships; (vi) the intellectual property coverage and positions of CRISPR Therapeutics, its licensors and third parties as well as the status and potential outcome of proceedings involving any such intellectual property; (vii) the sufficiency of CRISPR Therapeutics cash resources; and (viii) the therapeutic value, development, and commercial potential of CRISPR/Cas9 gene editing technologies and therapies including as compared to other therapies. Without limiting the foregoing, the words believes, anticipates, plans, expects and similar expressions are intended to identify forward-looking statements. You are cautioned that forward-looking statements are inherently uncertain. Although CRISPR Therapeutics believes that such statements are based on reasonable assumptions within the bounds of its knowledge of its business and operations, forward-looking statements are neither promises nor guarantees and they are necessarily subject to a high degree of uncertainty and risk. Actual performance and results may differ materially from those projected or suggested in the forward-looking statements due to various risks and uncertainties. These risks and uncertainties include, among others: the potential for initial and preliminary data from any clinical trial and initial data from a limited number of patients not to be indicative of final trial results; the potential that clinical trial results may not be favorable; that one or more of CRISPR Therapeutics internal or external product candidate programs will not proceed as planned for technical, scientific or commercial reasons; that future competitive or other market factors may adversely affect the commercial potential for CRISPR Therapeutics product candidates; uncertainties inherent in the initiation and completion of preclinical studies for CRISPR Therapeutics product candidates (including, without limitation, availability and timing of results and whether such results will be predictive of future results of the future trials); uncertainties about regulatory approvals to conduct trials or to market products; the potential impacts due to the coronavirus pandemic such as (x) delays in regulatory review, manufacturing and supply chain interruptions, adverse effects on healthcare systems and disruption of the global economy; (y) the timing and progress of clinical trials, preclinical studies and other research and development activities; and (z) the overall impact of the coronavirus pandemic on its business, financial condition and results of operations; uncertainties regarding the intellectual property protection for CRISPR Therapeutics technology and intellectual property belonging to third parties, and the outcome of proceedings (such as an interference, an opposition or a similar proceeding) involving all or any portion of such intellectual property; and those risks and uncertainties described under the heading "Risk Factors" in CRISPR Therapeutics most recent annual report on Form 10-K, quarterly report on Form 10-Q, and in any other subsequent filings made by CRISPR Therapeutics with the U.S. Securities and Exchange Commission, which are available on the SEC's website at http://www.sec.gov. Existing and prospective investors are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date they are made. CRISPR Therapeutics disclaims any obligation or undertaking to update or revise any forward-looking statements contained in this press release, other than to the extent required by law.

Investor Contact:Susan Kim+1-617-307-7503susan.kim@crisprtx.com

Media Contact:Rachel Eides+1-617-315-4493rachel.eides@crisprtx.com

CRISPR Therapeutics AGCondensed Consolidated Statements of Operations(Unaudited, In thousands except share data and per share data)

Three Months Ended September 30,

Nine Months Ended September 30,

2021

2020

2021

2020

Revenue:

Collaboration revenue

$

329

$

148

$

900,733

$

349

Grant revenue

495

1,331

Total revenue

$

824

$

148

$

902,064

$

349

Operating expenses:

Research and development

105,321

71,008

304,163

184,581

General and administrative

24,352

21,539

78,675

62,442

Total operating expenses

129,673

92,547

382,838

247,023

(Loss) income from operations

(128,849

)

(92,399

)

519,226

(246,674

)

Total other income, net

1,101

160

3,806

5,804

Net (loss) income before income taxes

(127,748

)

(92,239

)

523,032

(240,870

)

Benefit (provision) for income taxes

595

Continued here:
CRISPR Therapeutics Provides Business Update and Reports Third Quarter 2021 Financial Results - Yahoo Finance

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ORGANICELL REGENERATIVE MEDICINE, INC. : Entry into a Material Definitive Agreement, Unregistered Sale of Equity Securities, Financial Statements and…

Sunday, November 7th, 2021

Item 1.01 Entry into a Material Definitive Agreement.

On October 29, 2021, the Company entered into an Exchange Agreement (the"Exchange Agreement") with shareholders who were issued shares under (i) variousconsulting and employment agreements during 2021 (the "Service Providers"), and(ii) those shareholders who were issued shares of common stock pursuant to theCompany's Management and Consultants Performance Stock Plan (the "MCP Plan")(each person who received shares pursuant to the MCP Plan is referred to as an"MCP Plan Holder").

The Service Providers who executed the Exchange Agreement were issued a total of30,300,000 shares under their respective consulting or employment agreements(the "Service Provider Shares"), and the MCP Plan Holders who executed theExchange Agreement received a total of 49,500,000 shares under the MCP Plan, foran aggregate of 79,800,000 shares of common stock. As of the effective date ofthe Agreement, the Service Providers and MCP Plan Holders who executed theExchange Agreement agreed to exchange their respective Service Provider Sharesor the shares issued under the MCP Plan for newly issued shares pursuant to theCompany's newly formed 2021 Equity Incentive Plan (the "EIP"), on a 1:1 basis,resulting in the issuance of 79,800,000 shares of common stock under the EIP(the "Exchange Shares").

The Exchange Agreement contains certain customary representations, warranties,and covenants for transactions of this type.

The description of the Exchange Agreement does not purport to be complete and isqualified in its entirety by reference to the full text of the form of ExchangeAgreement which is attached as Exhibit 10.1 to this Current Report on Form8-K and is incorporated herein by reference.

Item 3.02 Unregistered Sales of Equity Securities.

The disclosure set forth above in Item 1.01 of this Current Report on Form 8-Kwith respect to the issuances of the Exchange Sharers pursuant to the ExchangeAgreement is incorporated by reference into this Item 3.02.

The Exchange Shares were issued in reliance on the exemption from registrationrequirements thereof provided by Section 4(a)(2) of the Securities Act.

Item 9.01 Financial Statements and Exhibits.

* Schedules, exhibits and similar attachments have been omitted pursuant to Item601(a)(5) of Regulation S-K. The Company hereby undertakes to furnish copies ofsuch omitted materials supplementally upon request by the U.S. Securities andExchange Commission.

1

Edgar Online, source Glimpses

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ORGANICELL REGENERATIVE MEDICINE, INC. : Entry into a Material Definitive Agreement, Unregistered Sale of Equity Securities, Financial Statements and...

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Blood Thawing System Market to Witness Massive Revenue Streams from Growing Demand for Rapid Dry Plasma Thawing Products for FFPs in Blood Banks,…

Sunday, November 7th, 2021

ALBANY, N.Y., Nov. 3, 2021 /PRNewswire/ -- Advancements in blood thawing devices have pivoted on the changing requirements of fresh frozen plasma (FFP) in transfusion practices and thawing procedures in cryopreservation. Plasma thawers to maintain the integrity of FFPs are growing in applications in laboratories, blood banks, and hospital settings. New procedures and technologies have been introduced in the blood thawing system market, which prevent potential risks of contamination. Particularly, the adoption of dry bathing systems for preventing transfusion-associated bacterial sepsis in treating blood disorders and cancer is gaining momentum.

The use of FDA-approved, CE-marked, and ISO certified plasma thawers are gaining popularity in umbilical cord blood processing and cell-based therapies, thereby enriching the prospects of regenerative medicine. The need for new device designs and software for temperature controllers occupies a key role in improving the existing cryopreservation protocols, which has opened up a lucrative avenue for players, notes the study on the blood thawing systems market.

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Dry plasma thawing products are gaining preference over traditional water baths or wet plasma thawers, as they help increase the success of transfusion of adult stem cells. Asia Pacific is a highly lucrative market, where the players have gained opportunities from rising on-demand cell thawing to successfully deliver cell-based therapies to target population. The global valuation of the blood thawing system market is projected to reach US$ 400 Mn by 2030, at a CAGR of 7.7% during the forecast period.

Key Findings of Blood Thawing System Market Study

GMP-compliant Equipment Improve Safety and Effectiveness of Thawing Processes: End users have become increasingly aware about Good Manufacturing Practice (GMP), manufacturer's instructions, and other guidelines for preparing FFPs for use in various applications of transfusion medicine. Most prominently, the risk of transfusion-associated bacterial sepsis has led to constant technological advancements in the blood thawing equipment to ensure the efficacy of the thawing method. GMP-ready cryochain hardware and software are gaining traction in umbilical cord blood processing, finds a TMR study on the blood thawing system market.

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The success of cryopreservation is dependent on appropriate execution of thawing procedures. Indeed, advances made in the protocols for on-demand thawing in regenerative medicine have bolstered the prospects of the blood thawing system market.

Regulatory Approval of Next-generation Thawing Devices Extends Horizon: The need for eliminating continuous blood products manufacturing is a key underpinning for adopting reliable thawing processes. In this light, thawing equipment for rapid, reliable thawing of FFP is garnering attention of clinicians for use in patients in emergency setting as well as for meeting the demand in planned hospitalizations.

Next-gen plasma thawing devices promise low turnaround time, are of portable designs, and ensure high throughput. The use of such devices is expected to rise in various applications in exchange transfusions, stem cell transfusions, and crystalloid infusion solutions.

TMR offers custom market research services that help clients to get information on their business scenario required where syndicated solutions are not enough, Request for Custom Research- https://www.transparencymarketresearch.com/sample/sample.php?flag=CR&rep_id=81455

Blood Thawing System Market: Key Drivers

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Blood Thawing System Market: Regional Dynamics

Blood Thawing System Market: Key Players

Some of the key players in the blood thawing system market are Sartorius AG, Thermo Fisher Scientific, Inc., Cytiva (GE Healthcare), Cardinal Health, KW Scientific Apparatus Srl, Boekel Scientific, Barkey GmbH & Co. KG, Helmer Scientific Inc., and Fremon Scientific Inc.

Global Blood Thawing System Market: Segmentation

Modernization of healthcare in terms of both infrastructure and services have pushed the healthcare industry to new heights, Stay Updated with Latest Healthcare Industry Research Reportsby Transparency Market Research:

Blood Purification Equipment Market: Increasing knowledge and understanding of pathophysiology and hematology due to additional research and development coupled with noteworthy progress in bio separation techniques are some of the other factors contributing to the overall growth of the global blood purification equipment market

Autoimmune Disease Diagnostics Market: Increasing awareness and knowledge about autoimmune diseases among patients and care-givers would significantly contribute to the growth of the autoimmune disease diagnostics market. Rising awareness among people and increasing government initiatives are the major factors driving the autoimmune disease diagnostics market

Capillary and Venous Blood Sampling Devices Market: Manufacturers in the capillary and venous blood sampling devices market are increasing their focus to develop COVID-19 rapid test kits that are suitable for qualitative detection of the novel coronavirus using finger-prick samples. Companies are increasing efforts to innovate in small volume blood collection devices that are being made available for retail pharmacies.

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Our data repository is continuously updated and revised by a team of research experts, so that it always reflects the latest trends and information. With a broad research and analysis capability, Transparency Market Research employs rigorous primary and secondary research techniques in developing distinctive data sets and research material for business reports.

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Sangamo Therapeutics Reports Recent Business and Clinical Highlights and Third Quarter 2021 Financial Results – Yahoo Finance

Sunday, November 7th, 2021

Conference Call and Webcast Scheduled for 9:15 a.m. Eastern Time

BRISBANE, Calif., November 04, 2021--(BUSINESS WIRE)--Sangamo Therapeutics, Inc. (Nasdaq: SGMO), a genomic medicine company, today reported third quarter financial results and provided business and clinical highlights.

"We are delighted to share clinical data and business updates across several programs demonstrating that Sangamo has three important assets progressing toward late-stage development. Our gene therapy portfolio is advancing with accumulating safety and efficacy data in our Fabry and hemophilia A programs, and preliminary proof-of-concept data demonstrate the clinical potential of our zinc finger genome engineering technology in sickle cell disease. These data readouts show the progression of our first-generation genomic medicine pipeline and potentially pave the way for new treatments. Our next generation programs focus on genome regulation and allogeneic CAR-Treg cell therapy, where we have a robust preclinical pipeline in neurological and autoimmune diseases. We are energized by this momentum and look forward to continued execution of our corporate strategy," said Sandy Macrae, Chief Executive Officer of Sangamo.

Recent Clinical and Business Highlights

Fabry Disease First four patients dosed exhibited above normal -Gal A activity; Phase 3 planning initiated

Earlier today, we announced preliminary clinical data from the first four patients treated in our Phase 1/2 STAAR study evaluating isaralgagene civaparvovec, or ST-920, our wholly owned Fabry disease gene therapy product candidate. Data as of the September 17, 2021 cutoff date from the four patients in the first two dose cohorts showed that isaralgagene civaparvovec was generally well tolerated. All four patients exhibited above normal alpha-galactosidase A (-Gal A) activity, which was maintained for up to one year for the first patient treated and through 14 weeks for the most recently treated patient. Activity of 2-fold to 15-fold above mean normal was observed at last measurement as of the cutoff date. Withdrawal from enzyme replacement therapy (ERT) has taken place for one patient and is planned for the other patient on ERT, based on the stability of their -Gal A activity following treatment.

The fifth patient in the STAAR study, who is the first patient in the third cohort (3e13vg/kg), was dosed after the cutoff date. The sixth patient is currently in screening also for the third dose cohort. We expect to provide updated data throughout 2022 and present these results at a medical meeting.

Based on the STAAR study results to date, we have initiated planning for a Phase 3 Fabry disease clinical trial.

Sickle Cell Disease Preliminary-proof-of-concept data will be presented at ASH as clinical program advances

Story continues

Preliminary proof-of-concept results from the Phase 1/2 PRECIZN-1 study investigating SAR445136, formerly BIVV003, an investigational zinc finger nuclease gene edited cell therapy, in patients with severe sickle cell disease (SCD) will be presented at the 63rd Annual Meeting of the American Society of Hematology (ASH) on December 12, 2021. Results as of the June 25, 2021 cutoff date show that all four treated patients did not require blood transfusions post engraftment and had no adverse or serious adverse events related to SAR445136 through 65 weeks of follow-up for the longest treated patient. The four treated patients all experienced increases in total hemoglobin, fetal hemoglobin and percent F cells.

We and Sanofi continue to advance the sickle cell disease program. We recently obtained manufacturing requirements guidance from FDA in preparation for further potential clinical studies. Separately, we and Sanofi made the business decision to cease development of the beta thalassemia indication in order to focus resources on the sickle cell disease program. ST-400 for beta thalassemia was developed with the support of a grant from the California Institute for Regenerative Medicine (CIRM).

Hemophilia A Four patients at highest dose experienced mean FVIII activity of 30.9% at week 104

Updated follow-up results from the Phase 1/2 Alta study of giroctocogene fitelparvovec gene therapy in patients with severe hemophilia A will be presented at ASH on December 12, 2021. For the four patients in the highest dose 3e13vg/kg cohort who have reached 104 weeks of follow-up as of the May 19, 2021 cutoff date, mean Factor VIII (FVIII) activity was 30.9% at week 104 as measured by chromogenic assay. In this cohort, the annualized bleeding rate was zero for the first year after treatment and 0.9 throughout total duration of follow-up. Giroctocogene fitelparvovec was generally well tolerated.

We and Pfizer also announced that some of the patients treated in the Phase 3 AFFINE trial of giroctocogene fitelparvovec experienced FVIII activity greater than 150% following treatment. None of these patients have experienced thrombotic events and some have been treated with direct oral anticoagulants to reduce thrombotic risk. Pfizer voluntarily paused screening and dosing of additional patients in the trial to implement a protocol amendment intending to provide guidance regarding the management of patients with FVIII levels that exceed 150%. On November 3, 2021, Pfizer was informed that the FDA has put this trial on clinical hold. The next step is to share the proposed protocol amendment with health authorities and respond to the clinical hold, after which the Companies will be able to provide updated timing for the trial.

Renal Transplant First patient enrolled, expect two patients to be dosed by mid-2022

The first patient has been enrolled in our Phase 1/2 STEADFAST study evaluating TX200, our wholly owned autologous HLA-A2 CAR Treg cell therapy product candidate treating patients receiving an HLA-A2 mismatched kidney from a living donor. We expect the first two patients in this study to be dosed by the middle of 2022 following kidney transplantation. We continue to open study sites and screen patients.

Research, Manufacturing, and Corporate Updates

Biogen announced type 1 myotonic dystrophy (DM1) as the previously undisclosed neuromuscular preclinical target in our collaboration.

We recently completed and brought online our in-house cell therapy manufacturing facility in our Brisbane, California headquarters and remain on track to complete our in-house cell therapy manufacturing facility in Valbonne, France by year-end.

We appointed D. Mark McClung as Chief Operating Officer, an important organizational step to support the multiple advancing wholly owned and partnered programs.

Third Quarter 2021 Financial Results

Consolidated net loss attributable to Sangamo for the third quarter ended September 30, 2021 was $47.7 million, or $0.33 per share, compared to a net loss attributable to Sangamo of $1.6 million, or $0.01 per share, for the same period in 2020.

Revenues

Revenues for the third quarter ended September 30, 2021, were $28.6 million, compared to $57.8 million for the same period in 2020, a decrease of $29.2 million.

The reduction in revenue was primarily due to a $39.3 million decrease related to our giroctocogene fitelparvovec and C9ORF72 collaboration agreements with Pfizer, resulting from the completion of our activities in 2020, and a $2.3 million decrease related to our collaboration agreement with Sanofi. These decreases were partially offset by higher revenues of $11.5 million and $1.3 million related to our collaboration agreements with Novartis and Biogen, respectively.

GAAP and Non-GAAP operating expenses

Three Months EndedSeptember 30,

Nine Months EndedSeptember 30,

(In millions)

2021

2020

2021

2020

Research and development

$

62.5

$

45.3

$

179.0

$

128.3

General and administrative

14.5

16.2

47.1

50.2

Total operating expenses

77.0

61.5

226.1

178.5

Stock-based compensation expense

(7.9

)

(6.7

)

(24.9

)

(19.1

)

Non-GAAP operating expenses

$

69.1

$

54.8

$

201.2

$

159.4

Total operating expenses on a GAAP basis for the third quarter ended September 30, 2021 were $77.0 million compared to $61.5 million for the same period in 2020. Non-GAAP operating expenses, which exclude stock-based compensation expense, for the third quarter ended September 30, 2021 were $69.1 million compared to $54.8 million for the same period in 2020.

The increase in total operating expenses on a GAAP basis was primarily driven by our higher clinical and manufacturing supply expenses along with our increased headcount to support the advancement of our clinical trials and our ongoing collaborations.

Cash, cash equivalents and marketable securities

Cash, cash equivalents and marketable securities as of September 30, 2021 were $519.0 million compared to $692.0 million as of December 31, 2020.

Revised Financial Guidance for 2021

We are revising our full-year operating expense guidance initially provided on February 24, 2021 and reiterated most recently on August 5, 2021 as follows:

(in millions)

Initially Provided February 24, 2021;Reiterated May 4, 2021and August 5, 2021

Updated on November 4, 2021

Estimated GAAP Operating Expenses

$285 to $305

$300 to $310

Estimated Non-GAAP Operating Expenses

$255 to $275*

$265 to $275**

*excludes estimated stock-based compensation of $30 million

**excludes estimated stock-based compensation of $35 million

Conference Call

Sangamo will host a conference call today, November 4, 2021, at 9:15 a.m. Eastern Time, which will be open to the public. The call and live Q&A will be webcast.

The conference call dial-in numbers are (877) 377-7553 for domestic callers and (678) 894-3968 for international callers. The conference ID number for the call is 5178059. Participants may access the live webcast via a link on the Sangamo Therapeutics website in the Investors and Media section under Events and Presentations. Call replay will be available for one week following the conference call. The conference call replay numbers for domestic and international callers are (855) 859-2056 and (404) 537-3406, respectively. The conference ID number for the replay is 5178059.

About Sangamo Therapeutics

Sangamo Therapeutics is a clinical-stage biopharmaceutical company with a robust genomic medicines pipeline. Using ground-breaking science, including our proprietary zinc finger genome engineering technology and manufacturing expertise, Sangamo aims to create new genomic medicines for patients suffering from diseases for which existing treatment options are inadequate or currently dont exist. For more information about Sangamo, visit http://www.sangamo.com.

Forward-Looking Statements

This press release contains forward-looking statements regarding our current expectations. These forward-looking statements include, without limitation, statements relating to the therapeutic and commercial potential of our product candidates, the anticipated plans and timelines of Sangamo and our collaborators for screening, enrolling and dosing patients in and conducting our ongoing and potential future clinical trials and presenting clinical data from our clinical trials, the anticipated advancement of our product candidates to late-stage development including potential future Phase 3 trials, anticipated implementation of a protocol amendment for the Phase 3 AFFINE clinical trial of giroctocogene fitelparvovec and the resumption of the dosing of additional patients in the trial; our revised 2021 financial guidance related to GAAP and non-GAAP total operating expenses and stock-based compensation; our continued execution of our corporate strategy; the anticipated completion of our in-house cell therapy manufacturing facility in Valbonne, France; and other statements that are not historical fact. These statements are not guarantees of future performance and are subject to certain risks and uncertainties that are difficult to predict. Factors that could cause actual results to differ include, but are not limited to, risks and uncertainties related to the effects of the evolving COVID-19 pandemic and the impacts of the pandemic on the global business environment, healthcare systems and business and operations of Sangamo and our collaborators, including the initiation and operation of clinical trials; the research and development process, including the enrollment, operation and results of clinical trials and the presentation of clinical data; the uncertain timing and unpredictable nature of clinical trials and clinical trial results, including the risk that any protocol amendment for the Phase 3 AFFINE trial of giroctocogene fitelparvovec may not be accepted by the relevant review bodies in a timely manner, or at all, or that the FDA may not lift its clinical hold on the Phase 3 AFFINE trial in a timely manner, or at all, each of which could further delay or preclude further patient dosing in the trial as well as the risks that therapeutic effects observed in clinical trial results will not be durable in patients and that final clinical trial data will not validate the safety and efficacy of our product candidates; reliance on results of early clinical trials, which results are not necessarily predictive of future clinical trial results; our limited experience manufacturing biopharmaceutical products, including the risks that we may be unable to maintain compliant manufacturing facilities, build additional facilities and manufacture our product candidates as intended; and our ability to achieve expected future financial performance.

There can be no assurance that we and our collaborators will be able to develop commercially viable products. Actual results may differ materially from those projected in these forward-looking statements due to the risks and uncertainties described above and other risks and uncertainties that exist in the operations and business environments of Sangamo and our collaborators. These risks and uncertainties are described more fully in our Securities and Exchange Commission filings and reports, including in our Annual Report on Form 10-K for the year ended December 31, 2020 as supplemented by our Quarterly Report on Form 10-Q for the quarter ended September 30, 2021. Forward-looking statements contained in this announcement are made as of this date, and we undertake no duty to update such information except as required under applicable law.

Non-GAAP Financial Measure

To supplement our financial results and guidance presented in accordance with GAAP, we present non-GAAP total operating expenses, which exclude stock-based compensation expense from GAAP total operating expenses. We believe that this non-GAAP financial measure, when considered together with our financial information prepared in accordance with GAAP, can enhance investors and analysts ability to meaningfully compare our results from period to period and to our forward-looking guidance, and to identify operating trends in our business. We have excluded stock-based compensation expense because it is a non-cash expense that may vary significantly from period to period as a result of changes not directly or immediately related to the operational performance for the periods presented. This non-GAAP financial measure is in addition to, not a substitute for, or superior to, measures of financial performance prepared in accordance with GAAP. We encourage investors to carefully consider our results under GAAP, as well as our supplemental non-GAAP financial information, to more fully understand our business.

SELECTED CONSOLIDATED FINANCIAL DATA

(unaudited; in thousands, except per share data)

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Cryoport Reports Record Third Quarter and Nine Months Revenue for 2021 – PRNewswire

Sunday, November 7th, 2021

NASHVILLE, Tenn., Nov. 4, 2021 /PRNewswire/ --Cryoport, Inc. (NASDAQ: CYRX) ("Cryoport" or the "Company"),a global leader in temperature-controlled supply chain solutions for the life sciences industry,today announced financial results for the three- and nine-month periods ended September 30,2021.

Jerrell Shelton, CEO of Cryoport, commented, "We delivered an outstanding third quarter and nine months of the year for the Company with strength across the board in all areas of our business. During the third quarter, our total revenue grew to a record $56.7 million driven by 38% organic growth year-over-year from Cryoport Systems and CRYOGENE and continuing strong revenue performance by MVE Biological Solutions and CRYOPDP. Our robust performance was driven by superlative execution by our global teams across all our business units. Our markets are strong and growing. Demand for MVE Biological Solutions' products remained at record highs, Cryoport Systems added 38 new customers during the quarter, and we successfully expanded the footprints for both CRYOPDP and CRYOGENE.

"Our Biopharma/Pharma revenue increased 371% year over year in the third quarter of 2021 or 41%, organically. But the story does not end there, we now support a record 582 clinical trials, compared with 561 at the end of the second quarter of 2021 and 517 at the end of the third quarter of 2020. We also support eight commercial therapies in regenerative medicine, including Novartis' KYMRIAH, Gilead/Kite's YESCARTAand TECARTUS, bluebird bio's ZYNTEGLO andSKYSONA, Bristol Myers Squibb's BREYANZI and ABECMA and Orchard Therapeutics' LIBMELDY. Additionally, four of the approved therapies received extended or supplemental approvals in the third quarter.

"Our revenue by market for the three- and nine-months ended September 30, 2021, as compared to the same periods in 2020 was asfollows:

Cryoport, Inc. and Subsidiaries

Total revenues by market

(unaudited)

Three Months Ended September 30,

Nine Months Ended September 30,

(in thousands)

2021

2020

% Change

2021

2020

% Change

Biopharma/Pharma

$ 46,001

$ 9,760

371%

$ 133,878

$ 27,120

394%

Animal Health

8,261

223

3598%

25,655

664

3762%

Reproductive Medicine

2,431

1,189

105%

6,635

2,551

160%

Total revenues

$ 56,693

$ 11,172

407%

$ 166,168

$ 30,335

448%

"Our solutions are experiencing accelerating global demand as a record number of cell and gene therapies are slated for commercialization in the coming months and years."

Mr. Shelton concluded, "We continue to set the pace and the standard for supply chain solutions for the regenerative medicine industry which continues to be in its very early stages of development. To support our continued global growth, we have expanded into 33 facilities in 16 countries and have initiated further expansion within the fast-growing Asia-Pacific (APAC) and EMEA (Europe, Middle East, and Africa) regions.We believe our strong momentum will continue to build through the remainder of the year and beyond as we realize the large commercial revenue potential of our vast pipeline of clinical trials supported. Our performance is a testament to the power of our strategy and our team's commitment to Cryoport and its mission, and, with that, we expect significant worldwide opportunities ahead to continue building sustainable, long-term value for shareholders."

Biopharma/Pharma

Our total Biopharma/Pharma revenue increased by $36.2 million, or 371%, to $46.0 million for the third quarter of 2021 compared to $9.8 million for the third quarter of 2020, driven by strong revenue contributions from all business units. For the third quarter of 2021, Biopharma/Pharma revenue grew organically by $4.0 million, or 41%, to $13.8 million compared to third quarter in the prior year.

As of the end of the third quarter, we supportedanettotalof582 clinical trials, compared with 561 at the end of the second quarter 2021 and 517 in third quarter 2020. The number of trials by phase and region are as follows:

Cryoport Supported Clinical Trials by Phase

Clinical Trials

September 30,

2021

2020

2019

Phase 1

240

207

180

Phase 2

272

244

191

Phase 3

70

66

54

Total

582

517

425

Cryoport Supported Clinical Trials by Region

Clinical Trials

September 30,

2021

2020

2019

Americas

459

411

360

EMEA

92

83

55

APAC

31

23

10

Total

582

517

425

A total of nine (9) Cryoport supported Biologic License Applications (BLAs) or Marketing Authorization Applications (MAAs) were filed in the nine months ended September 30, 2021, based on internal information and forecasts from the Alliance for Regenerative Medicine, of which three (3) were filed during the third quarter of 2021. Looking forward, we anticipate up to another four (4) BLA and MAA submissions for Cryoport-supported products during the remainder of 2021 and, at this time, an additional twenty-one (21) filings in 2022. Additionally, a total of four (4) Cryoport supported therapies received extended or supplemental approvals in the third quarter.

Animal Health

Our revenue from the Animal Health market increased by $8.0 million, or 3,598%, to $8.3 million for thethird quarter ended September 30, 2021,ascomparedtothesameperiodin2020 andwas primarily driven byouracquisitionofMVE Biological Solutions,whichhasastrongandlongstanding presenceinthismarket. Third quarter revenue grew organically by 31% over the prior year demonstrating successful execution of our engagement strategy within the animal health space.

Reproductive Medicine

Reproductive Medicine revenue more than doubled to $2.4 million for the third quarter of 2021 compared to $1.2 million for the third quarter of 2020, an increase of $1.2 million, or 105%. We see continuing strong demand for our CryoStork solutionprovided by Cryoport Systems driven by fertility clinic networks that are looking for global standardization on our best-in-class solution. MVE Biological Solutions also contributed revenue to our Reproductive Medicine market through its portfolio of cryogenic shipper and freezersolutions. We plan to continue to add agreements with new fertility clinics to our network globally during the remainder of 2021 and beyond to drive increased adoption of our services as well as expand our support efforts within this space to EMEA and APAC.

Financial Highlights

Note: All reconciliations of GAAP to adjusted (non-GAAP) figures above are detailed in the reconciliation tables included later in the press release.

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SanBio Announces Publication Comparing Outcome Measures for Persons With Chronic Traumatic Brain Injury in Expert Review of Neurotherapeutics -…

Sunday, November 7th, 2021

TOKYO & MOUNTAIN VIEW, Calif.--(BUSINESS WIRE)--The SanBio Group (SanBio Co., Ltd. of Tokyo, Japan , SanBio, Inc. of Mountain View, California, US, and SanBio Asia Pte. Ltd. of Singapore) (TOKYO:4592), hereby announce that data comparing outcome measures for persons with traumatic brain injury (TBI) living with chronic motor deficits was published in Expert Review of Neurotherapeutics.

Success in clinical trials in chronic TBI is challenging to define and measure; therefore, this publication is an important advancement for the field of research as it relates to the assessment of persons with motor deficits resulting from a TBI, said Michael A. McCrea, Co-Director, Center For Neurotrauma Research; Professor, Department Of Neurosurgery, Medical College Of Wisconsin, Milwaukee, USA; and lead author for the publication. This study supports the use of Disability Rating Scale (DRS) and Fugl-Meyer Motor Scale (FMMS) in the evaluation of long-term functional outcomes and motor impairment in future clinical trials of persons with chronic motor deficits secondary to TBI.

While acute TBI is widely assessed using Extended Glasgow Outcome Scale (GOS-E), this scale is less well-defined for persons who have chronic, or long-term, motor deficits as a result of their injury. The publication, entitled, Determining minimally clinically important differences (MCIDs) for outcome measures in patients with chronic motor deficits secondary to traumatic brain injury, determined MCIDs for DRS and FMMS. MCID is defined as the smallest change on a measure that is reliably associated with a meaningful change in a patient's clinical status, function, or quality of life.

Establishing MCIDs for the DRS and FMMS in chronic TBI provides improved precision for assessing long-term functional outcomes and motor impairment, respectively, as compared to the widely used GOS-E Scale, which is most appropriate for use in acute TBI. The findings of this study support the use of DRS and Fugl-Meyer Scales in the evaluation of clinical outcomes, and define the amplitude of clinically meaningful improvement for future chronic TBI clinical trials.

At SanBio, we are passionate about improving the lives of persons living with long-term motor deficits as a result of a TBI or stroke. This publication will help to overcome one of the most challenging areas of clinical research: determining the minimal improvement that would be clinically meaningful in patients with chronic motor deficit. We would like to extend our gratitude to the physicians and rehabilitation specialists who supported this important work, added, Bijan Nejadnik, M.D., Corporate Officer, Chief Medical Officer and Head of Research.

This retrospective analysis is from SanBios 1-year, double-blind, randomized, surgical sham-controlled, Phase 2 STEM cell therapy for TRAumatic brain injury (STEMTRA) trial (NCT02416492), in which persons with chronic motor deficits secondary to TBI (n=61) underwent intracerebral stereotactic implantation of SB623 or sham surgery. MCIDs for DRS and FMMS were triangulated with anchor-based, distribution-based, and Delphi panel estimates. The published Delphi panel results are available here. The MCIDs for DRS and FMMS were: 1) 1.5 points for the Disability Rating Scale; 2) 6.2 points for the Fugl-Meyer Upper Extremity Subscale; 3) 3.2 points for the Fugl-Meyer Lower Extremity Subscale; and 4) 8.4 points for the Fugl-Meyer Motor Scale in persons with chronic motor deficits secondary to TBI.

The full publication can be accessed here.

About the STEM cell therapy for TRAumatic brain injury (STEMTRA) Trial

STEMTRA was a 12-month, Phase 2, randomized, double-blind, surgical sham-controlled, global trial evaluating the efficacy and safety of SB623 compared to sham surgery in patients with stable chronic neurological motor deficits secondary to TBI (https://clinicaltrials.gov identifier: NCT02416492). In this study, SB623 cells were implanted directly around the site of brain injury. The primary endpoint was mean change from baseline in FMMS score at six months to measure changes in motor impairment.

To be eligible for this trial, patients (ages 18-75) must have been at least 12 months post-TBI and had a Glasgow Outcome Scale extended (GOS-E) score of 3-6 (e.g., moderate or severe disability). The STEMTRA trial treated 61 patients from 27 sites in the U.S., Japan and Ukraine.

In this study, SB623 met its primary endpoint, with patients treated with SB623 achieving an average 8.3-point improvement from baseline in the FMMS, versus 2.3-points in the control group, at 6 months (p=0.040). No new safety signals were identified, and the most commonly reported adverse event was headaches. The Group, based on the study results, aims to apply for manufacture and marketing approval for SB623 as a regenerative medicine product by utilizing Japans conditional and time-limited approval system for regenerative medicine products.

About Traumatic Brain Injury

Traumatic brain injury (TBI) is one of the leading causes of death and disability worldwide. The estimated global incidence of acute TBI during 2016 was 27 million cases, and the estimated global prevalence of chronic impairment secondary to TBI was 55.5 million cases. Overall, TBI and long-term motor deficits secondary to TBI significantly impair persons self-care, employability, and quality of life, and are major burdens on healthcare systems worldwide. In the United States, approximately 43% of surviving hospitalized persons with TBI experience long-term motor deficits, with 5.3 million people estimated to live with long-term motor deficits secondary to TBI.

About SB623

SB623 is a proprietary, cell-based investigational product made from allogeneic modified and cultured adult bone marrow-derived mesenchymal stem cells (MSCs) that undergo temporary genetic modification. Implantation of SB623 cells into injured nerve tissue in the brain is expected to trigger the brains natural regenerative ability to recover lost motor functions. SanBio is preparing to file a Biologics License Application with the Pharmaceuticals and Medical Devices Agency in Japan for SB623 for the treatment of chronic motor deficits resulting from TBI with STEMTRA results.

About SanBio Group (SanBio Co., Ltd., SanBio, Inc. and SanBio Asia Pte. Ltd.)

SanBio Group is engaged in the regenerative cell medicine business, spanning research, development, manufacture, and sales of regenerative cell medicines. The Companys propriety regenerative cell medicine product, SB623, is currently being investigated for the treatment of several conditions including chronic neurological motor deficit resulting from traumatic brain injury and stroke. The Company is headquartered in Tokyo, Japan, Mountain View, California, US, and SanBio Asia Pte. Ltd. of Singapore), and additional information about SanBio Group is available at https://sanbio.com/en/

Sources:Alves, et al, Why Does Brain Trauma Research Fail? World Neurosurg. (2019) 130:115-121.Selassie AW, et al. Incidence of long-term disability following traumatic brain injury hospitalization, U.S., 2003. J Head Trauma Rehabil 2008;23:123-31.James SL, et al. Global, regional, and national burden of traumatic brain injury and spinal cord injury, 1990-2016: a systematic analysis for the Global Burden of Disease Study 2016. Lancet Neurol 2019;18:56-87.Walker WC & Pickett TC. Motor impairment after severe traumatic brain injury: a longitudinal multicenter study. J Rehabil Res Dev 2007;44:975-82.

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Dendreon Pharmaceuticals and Shoreline Biosciences Announce CMC and Manufacturing Alliance to Advance the Future of iPSC Cellular Therapy – Business…

Sunday, November 7th, 2021

SEAL BEACH, Calif. & SAN DIEGO--(BUSINESS WIRE)--Dendreon Pharmaceuticals, a commercial-stage biopharmaceutical company and pioneer in the development of cellular immunotherapy, and Shoreline Biosciences, a biotechnology company developing allogeneic off-the-shelf, standardized, and targeted natural killer (NK) and macrophage cellular immunotherapies derived from induced pluripotent stem cells (iPSC) for cancer, today announced an alliance to advance the future of iPSC-derived cellular therapies.

The alliance leverages Dendreons extensive manufacturing, process development and end-to-end logistics expertise for the advancement of Shorelines pipeline of iPSC-derived cellular therapies. Dendreon is providing scalable cGMP manufacturing support for certain programs through clinical development and launch, enabling Shoreline to rapidly advance multiple products in parallel.

With more than a decade of proven expertise in cell therapy manufacturing and an established supply chain and logistics infrastructure, Dendreon is well positioned to support Shoreline in manufacturing from Phase I clinical trials through commercialization, said Maria Cho, Vice President of Business Development and Corporate Strategy. We are thrilled to partner with Shoreline to enable the future of cell therapy and change the way serious diseases are treated.

We are excited to partner with Dendreon, a leader in cell therapy, to manufacture cost-efficient, highly-scalable product candidates, said Mohammad El-Kalay, Ph.D., Senior VP & Head of CMC for Shoreline. Through our partnership with Dendreon, we are accelerating the commercialization of our next generation NK cell and macrophage products to bring scalable, allogeneic, off the shelf therapies to more patients in need.

About Dendreon

Dendreon is a commercial-stage biopharmaceutical company and end-to-end provider of manufacturing services for the cell therapy market. Dendreons flagship product, PROVENGE (sipuleucel-T), was the first FDA-approved immunotherapy made from a patients own immune cells and has been prescribed to over 40,000 men in the U.S. since 2010. Dendreon is headquartered in Seal Beach, Calif. For more information about Dendreons contract manufacturing services division, please visit https://www.dendreon.com/Partner-With-Us.

About Shorelines iPSC NK cell technology

Shoreline has developed a proprietary platform focused on iPSC-derived natural killer (NK) cells and macrophages that are optimized with precise and rational genetic reprogramming. The Shoreline NK cell and macrophage-based cell therapies are designed to provide an effective and efficient means for targeting and killing tumors as well as repairing tissue homeostasis. Shorelines approach, based on the advantage of its iPSC cell engineering and expansion, is being used to create a streamlined, affordable, and scalable manufacturing process that can deliver cell therapy treatments to patients in a more cost-effective, time-saving manner. Shorelines technology is at the forefront of regenerative medicine and is being used to develop potential therapies to treat a wide range of oncology indications.

About Shoreline Biosciences

Shoreline is dedicated to creating next-generation cellular immunotherapies for cancer that overcome the current limitations of first-generation cell therapy products. Shoreline is building a pipeline of natural killer (NK) cell and macrophage-cell therapy candidates derived from its deep expertise in iPSC differentiation methods and genetic reprogramming of disease relevant pathways. Shoreline has strategic partnerships with Kite, a Gilead Company, and BeiGene, a global biotechnology company, and is supported by high-quality institutional investors. Shoreline Biosciences is headquartered in San Diego, CA.

For more information, please visit https://shorelinebio.com/ and engage with us on LinkedIn.

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Heart Tissue in a Dish Reveals New Links Between Neurodegeneration and Heart Disease – Yahoo Finance

Sunday, November 7th, 2021

Findings led by experts in Seattle, San Francisco and Cincinnati suggest that some severe cases of heart failure have root causes surprisingly similar to neurodegenerative diseases like Alzheimers, Huntingtons and ALS.

CINCINNATI, Nov. 3, 2021 /PRNewswire/ -- One of the leading reasons why children and adults need heart transplants is a condition called dilated cardiomyopathy (DCM).

Model of mutant RBM20 differential splicing and P-body impacts in dilated cardiomyopathy. Proposed model for the impact of wild-type and mutant RBM20 on nuclear regulation of splicing based on RNA-Seq and eCLIP data as compared to cytoplasmic role of mutant RBM20 on P-body formation and 3UTR association with mRNAs implicated in granule formation.

Some cases of heart failure have root causes surprisingly similar to diseases like Alzheimers, Huntingtons and ALS.

Over time, sometimes quite rapidly, the heart's thick strong muscle tissue becomes thin and weak, causing the left ventricle to swell like a balloon. This makes the heart less able to squeeze efficiently, which can lead to blood clots, irregular heartbeats, and sometimes sudden death when the malfunctioning heart simply stops beating. The origins of cardiomyopathy are diverse, including viral infections, autoimmune diseases, toxic drug exposures, and dozens of gene mutations.

Now, a multi-disciplinary team of clinicians and researchers has deciphered the function of a specific genetic mutation that causes cardiomyopathy. Their findings, published Nov. 3, 2021, in Nature Communications, were made possible by growing gene-edited human heart tissue from induced pluripotent stem cells and measuring the activity, location and binding of this mutant protein.

The team was led by co-corresponding authors Charles Murry, MD, PhD, a regenerative medicine expert at the University of Washington; Bruce Conklin, MD, a genetic engineering expert with the Gladstone Institutes in California, and Nathan Salomonis, PhD, a computational genomics expert at Cincinnati Children's.

"We hope this study will lead to broader insights that could lead to improved heart failure therapies," Conklin says.

Cutting-edge experiments expose more of the heart's inner workings

Over the last several decades, the research community has made many discoveries that have led to improved medications and medical devices that can dramatically extend life by slowing down the progression of heart failure. However, we still lack proven cures.

Story continues

This study reveals a new mechanism of cardiomyopathy initiation by the RNA binding motif protein 20 (RBM20). This protein helps control RNA splicing in the heart, the process by which RNAs are sliced and diced to give rise to different proteins in different tissues. Normally, RBM20 splices RNAs to make proteins that enable the heart to adapt to stress and contract regularly throughout a person's entire life. But a class of mutations in RBM20 result in severe cardiomyopathy in adulthood.

"We and others had previously studied RBM20's function during heart development, but we had little to no clue of why it stops working in disease. We needed to step up our game if our research was to have a clinical impact," says Alessandro Bertero, PhD, who contributed to the work while at the University of Washington and now leads an Armenise-Harvard Laboratory at the University of Turin in Italy.

Discovering this protein's role was especially complex because knocking out this gene in animal models does not mimic the damaging effects seen in people. Instead, the work required editing the genome of healthy cells and engineering human heart tissue from these cells in a lab dish. Only by producing heart tissue similar to that found in humans could the authors understand the contractile defects and molecular mechanisms underlying this gene's function in a controlled manner.

"That was exactly what we intended when we started this project by genome-editing induced pluripotent stem cells," says co-leading author Yuichiro Miyaoka, PhD, of the Tokyo Metropolitan Institute of Medical Science.

First, the team observed that the engineered muscle tissue carrying the mutant form of RBM20 did not function like tissue engineered with normal RBM20 or lacking the protein all together. The mutated muscle fibers contracted with significantly less force and upstroke velocity, much like a heart affected by cardiomyopathy.

Then, at the single-cell level, the team detected another important clue. Normally, RBM20 is located exclusively within the cell nucleus. However, the mutated form localizes almost entirely out of the nucleus, in the cell's cytoplasm.

This, by itself, did not mean muchuntil the cell was exposed to heavy stress. When that occurred, the mutant protein was detected within tiny "stress granules" made of protein and RNA that cells rapidly produce as a reaction to stress. In contrast, RBM20 in healthy cells remained within the nucleus and distinct from stress granules. This suggests there are additional cellular mechanisms, along with changes in splice-activity, leading to RBM20 cardiomyopathy.

"When the RNA binding landscape of mutant RBM20 was revealed by a technology called enhanced CLIP, it mimicked the binding of other splicing factors that have been implicated in neurodegenerative diseases. These factors, when mutated, also change their activity from RNA splicing to RNA aggregation outside the nucleus," says co-author Gene Yeo, PhD, MBA, a member of the Department of Cellular and Molecular Medicine at the University of California San Diego.

"Over time, such aggregates play havoc with other cell functions, ultimately leading to the tissue-weakening of heart muscle during cardiomyopathy," Salomonis says.

"It is intriguing to note the parallels between our observations with RBM20 and recent findings in neuro-degeneration," the paper states. "Indeed, recent work has hypothesized cytoplasmic RBM20 may be similar to the cytoplasmic RNP granules associated with neurodegeneration (Schneider et al., 2020), such as TAU for Alzheimer s disease, Huntingtin for Huntington s disease, and FUS for amyotrophic lateral sclerosis (ALS)."

Next steps

Co-authors for this study also included scientists from the University of Cincinnati Department of Electrical Engineering and Computer Science, Sana Biotechnology, and the University of California San Francisco.

The co-authors say the 3D heart tissue model they've developed has the potential to be used to test new drugs to block the formation of cytoplasmic granules as a possible treatment for cardiomyopathy, even those without RBM20 mutations.

"RBM20 has been a frustrating protein to study, as animal models don't fully recapitulate human disease pathology," says lead author Aidan Fenix, PhD. "It's exciting to now have an in vitro human cell model of RBM20 cardiomyopathy that shows the major clinical feature of dilated cardiomyopathy--reduced contractile force. We hope these models will speed the discovery of therapies to treat RBM20 dilated cardiomyopathy."

About this study

This work was supported by grants from the National Heart, Lung, and Blood Institute (U01 HL099997, P01 HL089707, R01 HL130533, F32 HL156361-01, HL149734, R01 HL128362, R01 HL128368, R01 HL141570, R01 HL146868); the National Institute of Diabetes and Digestive and Kidney (U54DK107979-05S1); the National Science Foundation (NSF CMMI-1661730); a JSPS Grant-in-Aid for Young Scientists, and grants from NOVARTIS, the Mochida Memorial Foundation, SENSHIN Medical Research Foundation, Naito Foundation, Uehara Memorial Foundation, a Gladstone-CIRM Fellowship, and the A*STAR International Fellowship.

Cision

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SOURCE Cincinnati Children's Hospital Medical Center

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3D printing vendors poised to benefit long term from supply chain disruptions – ZDNet

Sunday, November 7th, 2021

Supply chain woes are a headache for multiple industries, and the tech sector is no different amid semiconductor and component shortages and logistics disasters. The one exception may be 3D printing companies, which may actually benefit from supply chain challenges.

Stratasys' third-quarter earnings report hinted at an inflection point for 3D printing as supply chain issues are forcing manufacturers to rip up playbooks that have worked for decades. Offshore manufacturing doesn't look as good as it used to. Shipping costs are killing companies' margins, so you'll need more manufacturing closer to the customer. And inventory forecasting is a nightmare due to hoarding.

3D printing can alleviate a lot of these issues--as long as vendors can get enough inventory to make their own systems. Yoav Zeif, CEO of Stratasys, explained the supply chain challenges and opportunities well on the company's conference call.

We are one of those privileged industries there are not only suffering from the supply chain challenges, but also enjoying it long term because this is what brings to life the essence and the power of additive manufacturing. You want no more offshoring. You want to have digital inventory. You want to produce near the customer, and we see it every day in the level of engagement we have with the largest OEMs. We see that the world of manufacturing is going to change and be much more digitalized than what we see now.

Stratasys won't be the only one that may benefit from a shift from traditional supply chain practices to additive manufacturing.

Desktop Metal said it opened a new in-house manufacturing facility that will triple assembly space for its Production System platform. The upshot is that Desktop Metal is seeing pent-up demand for its Production System P-50 metal 3D printing platform.

3D Systems is also betting that additive manufacturing will see a demanding pop as enterprises look to make supply chains more flexible. 3D Systems has industrial use cases but has staked out healthcare and regenerative medicine as growth markets.

Lilach Payorski, CFO of Stratasys, said the third-quarter revenue growth of 24.3% was a sign of "the inflection point we are experiencing." "There was also strong performance from our manufacturing business, in particular, improvement from automotive and industrials in Europe," she said. Healthcare remains Stratasys' fastest growing business.

Stratasys reported revenue of $159 million with a net loss of $18.1 million, or 28 cents a share. Non-GAAP earnings were a penny a share. During the quarter, Stratasys landed a $20 million contract with the US Navy.

While in the long run, Stratasys can benefit from supply chain turmoil, Payorski said the company also has short-term issues like every other enterprise. She said:

We are carefully monitoring the ongoing macro issues of high global logistic costs and inflationary pricing of raw materials, which have pressured margins. Our top priority is to deliver our product in a timely manner. To help ensure this, we have increased production levels to offset sea and air delays in our planning process. We continue to evaluate a wide area of shipping options to ensure we can deliver goods with a minimal business impact.

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Global Regenerative Medicine Market (2021 to 2030) – by Product, Material, Application and Region – ResearchAndMarkets.com – Business Wire

Monday, August 30th, 2021

DUBLIN--(BUSINESS WIRE)--The "Regenerative Medicine Market by Product, by Material, by Application - Global Opportunity Analysis and Industry Forecast, 2021 - 2030" report has been added to ResearchAndMarkets.com's offering.

The global regenerative medicine market is expected to reach USD 172.15 billion by 2030 from USD 13.96 billion in 2020, at a CAGR of 28.9%.

Companies Mentioned

Regenerative Medicine are used to regenerate, repair, replace or restore tissues and organs damaged by diseases or due to natural ageing. These medicines help in the restoration of normal cell functions and are widely used to treat various degenerative disorders such as cardiovascular disorders, orthopedic disorders and others.

The rising demand for organ transplantation and increasing awareness about the use of regenerative medicinal therapies in organ transplantation along with implementation of the 21st Century Cures Act, a U.S. law enacted by the 114th United States Congress in December 2016 are creating growth opportunities in the market. However, high cost of treatment and stringent government regulations are expected to hinder the market growth.

The global regenerative medicine market is segmented based on product type, material, application, and geography. Based on product type, the market is classified into cell therapy, gene therapy, tissue engineering, and small molecule & biologic. Depending on material, it is categorized into synthetic material, biologically derived material, genetically engineered material, and pharmaceutical. Synthetic material is further divided into biodegradable synthetic polymer, scaffold, artificial vascular graft material, and hydrogel material. Biologically derived material is further bifurcated into collagen and xenogenic material. Genetically engineered material is further segmented into deoxyribonucleic acid, transfection vector, genetically manipulated cell, three-dimensional polymer technology, transgenic, fibroblast, neural stem cell, and gene-activated matrices. Pharmaceutical is further divided into small molecule and biologic. By application, it is categorized into cardiovascular, oncology, dermatology, musculoskeletal, wound healing, ophthalmology, neurology, and others. Geographically, it is analyzed across four regions, i.e., North America, Europe, Asia-Pacific, and RoW.

Key Topics Covered:

1. Introduction

2. Regenerative Medicine Market - Executive Summary

3. Porter's Five Force Model Analysis

4. Market Overview

4.1. Market Definition and Scope

4.2. Market Dynamics

5. Global Regenerative Medicine Market, by Product Type

5.1. Overview

5.2. Cell Therapy

5.3. Gene Therapy

5.4. Tissue Engineering

5.5. Small Molecules & Biologics

6. Global Regenerative Medicine Market, by Material

6.1. Overview

6.2. Synthetic Materials

6.3. Biologically Derived Materials

6.4. Genetically Engineered Materials

6.5. Pharmaceuticals

7. Global Regenerative Medicine Market, by Application

7.1. Overview

7.2. Cardiovascular

7.3. Oncology

7.4. Dermatology

7.5. Musculoskeletal

7.6. Wound Healing

7.7. Opthalomolgy

7.8. Neurology

7.9. Others

8. Global Regenerative Medicine Market, by Region

8.1. Overview

8.2. North America

8.3. Europe

8.4. Asia-Pacific

8.5. Rest of World

9. Company Profile

9.1. Integra Lifesciences Corporation

9.2. Abbvie Inc.

9.3. Merck Kgaa

9.4. Medtronic plc

9.5. Thermo Fisher Scientific Inc.

9.6. Smith+Nephew

9.7. Becton, Dickinson and Company

9.8. Baxter International Inc

9.9. Cook Biotech

9.10. Organogenesis Inc

For more information about this report visit https://www.researchandmarkets.com/r/nzud5i

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Global Regenerative Medicine Market (2021 to 2030) - by Product, Material, Application and Region - ResearchAndMarkets.com - Business Wire

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Global Cryopreservation Equipment Market Report 2021-2028 – Growing Acceptance for Regenerative Medicine & Increasing Needs of Biobanking…

Monday, August 30th, 2021

DUBLIN--(BUSINESS WIRE)--The "Cryopreservation Equipment Market Forecast to 2028 - COVID-19 Impact and Global Analysis by Type, Cryogen Type, Application, End User, and Geography" report has been added to ResearchAndMarkets.com's offering.

Freezers Segment to Contribute Major Share to Cryopreservation Equipment Market

Cryopreservation Equipment Market to reach US$ 11,255.02 million by 2028 from US$ 5,798.82 million in 2021; it is estimated to grow at a CAGR of 9.9%

The report highlights the trends prevailing in the market along with the market drivers and deterrents. The factors such as growing acceptance for regenerative medicine and increasing needs of biobanking practices drive the market growth. However, stringent regulatory requirements hinder the cryopreservation equipment market growth.

Cryopreservation plays an important part in the field of regenerative medicine as it facilitates stable and secure storage of cells and other related components for a prolonged time. Regenerative medicine enables replacing diseased or damaged cells, tissues, and organs by retrieving their normal function through stem cell therapy.

Owing to the advancements in the medical technology, stem cell therapy is now being considered as an alternative to traditional drug therapies in the treatment of a wide range of chronic diseases, including diabetes and neurodegenerative diseases.

Moreover, the US Food and Drug Administration (FDA) has approved blood-forming stem cells. The blood-forming stem cells are also known as hematopoietic progenitor cells that are derived from umbilical cord blood. The growing approvals for stem cell and gene therapies are eventually leading to the high demand for cryopreservation equipment. Following are a few instances of stem cell and gene therapies approved by the FDA and other regulatory bodies.

Based on type, the cryopreservation equipment market is segmented into freezers, sample preparation systems, and accessories. In 2020, the freezers segment held the largest share of the market, and it is expected to register the highest CAGR during 2021-2028. In ultracold freezers, liquid nitrogen is used for the successful preservation of more complex biological structures by virtually seizing all biological activities.

The COVID-19 pandemic has had a mixed impact on the cryopreservation equipment market. Restricted access to family planning services as well as diverted focus of people due to economic uncertainties and recession, and disturbed work-life balance have led to rise in egg and embryo freezing activities at fertility clinics during the pandemic.

As a result, the rising use of cryopreservation equipment is boosting the market growth. Furthermore, supply chain disruption caused due to congestion of ports and disturbances in other transport means has substantially affected the distribution of cryopreservation equipment and other accessories.

Market players are launching new and innovative products and services to maintain their position in the cryopreservation equipment market. In May 2021, Stirling Ultracold has been acquired by BioLife Solutions, Inc for cell and gene therapies and the broader biopharma market. In return for all of Stirling's outstanding shares, BioLife issued 6,646,870 shares of ordinary stock.

Key Market Dynamics

Market Drivers

Market Restraints

Market Opportunities

Future Trends

The report segments the global cryopreservation equipment market as follows:

By Type

By Cryogen Type

By Application

By End User

Companies Mentioned

For more information about this report visit https://www.researchandmarkets.com/r/tjgti5

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Global Cryopreservation Equipment Market Report 2021-2028 - Growing Acceptance for Regenerative Medicine & Increasing Needs of Biobanking...

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Worldwide Regenerative Medicine Industry to 2030 – Featuring AbbVie, Medtronic and Thermo Fisher Scientific Among Others – GlobeNewswire

Monday, August 30th, 2021

Dublin, Aug. 27, 2021 (GLOBE NEWSWIRE) -- The "Regenerative Medicine Market by Product, by Material, by Application - Global Opportunity Analysis and Industry Forecast, 2021 - 2030" report has been added to ResearchAndMarkets.com's offering.

The global regenerative medicine market is expected to reach USD 172.15 billion by 2030 from USD 13.96 billion in 2020, at a CAGR of 28.9%. Regenerative Medicine are used to regenerate, repair, replace or restore tissues and organs damaged by diseases or due to natural ageing. These medicines help in the restoration of normal cell functions and are widely used to treat various degenerative disorders such as cardiovascular disorders, orthopedic disorders and others.

The rising demand for organ transplantation and increasing awareness about the use of regenerative medicinal therapies in organ transplantation along with implementation of the 21st Century Cures Act, a U.S. law enacted by the 114th United States Congress in December 2016 are creating growth opportunities in the market. However, high cost of treatment and stringent government regulations are expected to hinder the market growth.

The global regenerative medicine market is segmented based on product type, material, application, and geography. Based on product type, the market is classified into cell therapy, gene therapy, tissue engineering, and small molecule & biologic. Depending on material, it is categorized into synthetic material, biologically derived material, genetically engineered material, and pharmaceutical. Synthetic material is further divided into biodegradable synthetic polymer, scaffold, artificial vascular graft material, and hydrogel material. Biologically derived material is further bifurcated into collagen and xenogenic material. Genetically engineered material is further segmented into deoxyribonucleic acid, transfection vector, genetically manipulated cell, three-dimensional polymer technology, transgenic, fibroblast, neural stem cell, and gene-activated matrices. Pharmaceutical is further divided into small molecule and biologic. By application, it is categorized into cardiovascular, oncology, dermatology, musculoskeletal, wound healing, ophthalmology, neurology, and others. Geographically, it is analyzed across four regions, i.e., North America, Europe, Asia-Pacific, and RoW.

The key players operating in the global regenerative medicine market include Integra Lifesciences Corporation, AbbVie Inc., Merck KGaA, Medtronic, Thermo Fisher Scientific Inc., Smith+Nephew, Becton, Dickinson and Company, Baxter International Inc, Cook Biotech, and Organogenesis Inc., among others.

Key Topics Covered:

1. Introduction

2. Regenerative Medicine Market - Executive Summary

3. Porter's Five Force Model Analysis

4. Market Overview4.1. Market Definition and Scope4.2. Market Dynamics

5. Global Regenerative Medicine Market, by Product Type5.1. Overview5.2. Cell Therapy5.3. Gene Therapy5.4. Tissue Engineering5.5. Small Molecules & Biologics

6. Global Regenerative Medicine Market, by Material6.1. Overview6.2. Synthetic Materials6.3. Biologically Derived Materials6.4. Genetically Engineered Materials6.5. Pharmaceuticals

7. Global Regenerative Medicine Market, by Application7.1. Overview7.2. Cardiovascular7.3. Oncology7.4. Dermatology7.5. Musculoskeletal7.6. Wound Healing7.7. Opthalomolgy7.8. Neurology7.9. Others

8. Global Regenerative Medicine Market, by Region8.1. Overview8.2. North America8.3. Europe8.4. Asia-Pacific8.5. Rest of World

9. Company Profile9.1. Integra Lifesciences Corporation9.2. Abbvie Inc.9.3. Merck Kgaa9.4. Medtronic plc9.5. Thermo Fisher Scientific Inc.9.6. Smith+Nephew9.7. Becton, Dickinson and Company9.8. Baxter International Inc9.9. Cook Biotech9.10. Organogenesis Inc

For more information about this report visit https://www.researchandmarkets.com/r/pl6r1p

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Worldwide Regenerative Medicine Industry to 2030 - Featuring AbbVie, Medtronic and Thermo Fisher Scientific Among Others - GlobeNewswire

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2 surgeons weigh in on the most promising areas of regenerative medicine – Becker’s Orthopedic & Spine

Monday, August 30th, 2021

Regenerative medicine is a growing area of orthopedic treatment. Two orthopedic surgeons told Becker's what they found the most exciting about its development.

Ask Orthopedic Surgeons is a weekly series of questions posed to orthopedic surgeons around the country about clinical, business and policy issues affecting orthopedic care. We invite all orthopedic surgeon and specialist responses.

Next week's question: How will joint replacement surgical robots improve in the next 10 years?

Please send responses to Carly Behm at cbehm@beckershealthcare.com by 5 p.m. CDT Tuesday, Aug. 31.

Note: Responses were edited for style.

Question: What area of regenerative medicine holds the most promise for orthopedics?

Mihir Patel, MD. OrthoIndy (Indianapolis): Regenerative medicine is a truly exciting frontier in medicine. In orthopedics, bone graft implants and substitutes are helping patients return to normal activities. The implants can be used in index operations as well as revisions for a variety of orthopedic procedures including acute stress reactions, stress fractures not conducive to metal fixation, and subchondral procedures. The evolution of orthopedic implants from metal to plastic, and now bone is improving outcomes for patients and broadening our arsenal as surgeons to help patients heal. The bone graft substitutes are reducing comorbidities of graft harvesting. Additionally, they are adding to the value proposition for patients who may have difficulty healing bone defects, nonunions, and osteoporosis.

Much like advances in cancer therapies over the past decade, bone graft substitutes have the potential for personalized, targeted medicine for these diagnoses as biomarkers become more available to help clinicians really pinpoint at the molecular level why some heal more quickly than others. Finally, regenerative medicine includes mostly outpatient procedures with sterile kits that are easily transported, giving orthopedic surgeons the confidence in the manufacturing and sterilization process.

Jason Snibbe, MD. Snibbe Orthopedics (Los Angeles): I think the use of biologics from plasma and bone marrow have the most promise right now to help a variety of injuries in orthopedics. We are able to help people recover without surgery and use their own tissue to heal, specifically in labral tears of the hip and meniscus tears in the knee.

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UC Davis and the School of Medicine set new records in research funding – UC Davis Health

Monday, August 30th, 2021

The University of California, Davis, set a new record for external research funding, receiving $968 million in awards in the fiscal year 2020-21, up $27 million from the previous record set last year. A major reason for this years growth was increased funding related to medicine and public health.

Professors Diana Farmer and Aijun Wang are collaborating to develop a stem cell treatment for spina bifida. (2019)

The School of Medicine received the largest increase in funding, up $92 million from the previous year, for a total of $368 million. Funding related to COVID-19 research totaled $42 million for the year. Studies in this area are providing critical insight into testing, vaccines, treatments and social impacts.

We are very proud of our researchers at the School of Medicine who rose to the challenge and expanded their groundbreaking work in the face of the pandemic, said Allison Brashear, dean of the UC Davis School of Medicine. All our research teams have shown great agility and collaboration across disciplines, quickly responding to emerging needs to prevent transmission and find treatments and vaccines to combat COVID-19, while also offering patients life-saving clinical trials in areas involving stem cell treatments, cancer and neuroscience, among many others.

Brashear noted that the School of Medicines clinical trials grew by 63% in the last year to $98 million.

The College of Agricultural and Environmental Sciences ($153 million), School of Veterinary Medicine ($83 million), College of Engineering ($80 million) and College of Biological Sciences ($58 million) rounded out the top five recipients.

This achievement reflects the unwavering commitment of our research community and their passion to address important societal needs during a year when operations were constrained due to the COVID-19 pandemic, Chancellor Gary S. May said. The societal impact of UC Davis research is far-reaching, spanning geographical boundaries and catering to diverse populations and needs.

The awards enable a broad range of research on topics including advancing human and animal health, protecting our planet and food supply and enabling a more resilient society.

The largest award, $51 million from the Department of Health and Human Services Centers for Disease Control and Prevention, went to Marc Schenker, distinguished professor of Public Health Sciences, to improve public health outcomes for all Californians by providing proper disease surveillance and prevention.

The federal government remains the largest provider of funding at $514 million, up $37 million from last year. The second leading source came from the state of California at $164 million, up $32 million. Funding from industry made up the third highest source, totaling $116 million, up $31 million.

UC Davis researchers received a total of 18 NSF CAREER Awards, a record for the university. These prestigious grants are offered to early-career faculty who have the potential to serve as academic role models in research and education and to lead advances in the mission of their department or organization.

Collaborative research bringing experts together from different fields of study continues to attract significant funding. These joint efforts often focus on addressing complex, large-scale challenges that require expertise from many perspectives.

We continue to see how multidisciplinary research provides a distinct advantage in tackling multifaceted issues, said Prasant Mohapatra, vice chancellor for Research at UC Davis. As one of the most academically comprehensive universities in the world, UC Davis offers a unique environment to solve these complex issues by bringing together experts from across our campuses.

Notable multidisciplinary awards include a $16 million grant from the National Institute of Mental Health for the UC Davis Conte Center to explore how infections in pregnancy lead to disorders in offspring. Principal investigators on this grant are Kimberly McAllister and Cameron Carter.

The Interdisciplinary Research and Strategic Initiatives division within the Office of Research offers support and resources to help teams advance their programs. Some of the notable interdisciplinary research projects include the work of Sheryl Catz, professor at the UC Davis Betty Irene Moore School of Nursing. Catz received $225,000 from the NIH National Cancer Institute for a project to improve the reach and effectiveness of smoking cessation services targeted to veterans living with HIV.

Diana Farmer, professor and chair in the Department of Surgery at UC Davis Health, also received $9 million from the California Institute for Regenerative Medicine (CIRM). Farmer is the principal investigator of the clinical trial, known formally as The CuRe Trial a cellular therapyfor in utero repair of myelomeningocele which uses stem cells before birth to treat the most serious form of spina bifida.

This story was originally written by Neelanjana Gautam and published here.

Note: Where funds are awarded up-front to cover several years, the money is counted in the first year the award was received. Incrementally funded awards are counted as authorized in each year. Reports are based on the principal investigators home school or college.

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UC Davis and the School of Medicine set new records in research funding - UC Davis Health

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These 4 tech breakthroughs could help end aging – Fast Company

Monday, August 30th, 2021

We live in a unique time when for the first time in human history there is a real opportunity to extend our lives dramatically. Recent scientific discoveries and technological breakthroughs that soon will translate into affordable and accessible life-extending tools will let us break the sound barrier of the current known record of 122 years. I am talking about breakthroughs in genetic engineering, regenerative medicine, healthcare hardware, and health data.

Very soon, slowing, reversing, or even ending aging will become a universally accepted ambition within the healthcare community. Technology is converging to make this a certainty. Developments in the understanding and manipulation of our genes and cells, in the development of small-scale health diagnostics, and in the leveraging of data for everything from drug discovery to precision treatment of disease are radically changing how we think about healthcare and aging.

When I speak of the Longevity Revolution, what I really mean is the cumulative effect of multiple breakthroughs currently underway across several fields of science and technology. Together, these parallel developments are forming the beginning of a hockey-stick growth curve that will deliver world-changing outcomes.

Completed in 2003, the Human Genome Project successfully sequenced the entire human genomeall 3 billion nucleotide base pairs representing some 25,000 individual genes. The project, arguably one of the most ambitious scientific undertakings in history, cost billions of dollars and took 13 years to complete. Today, your own genome can be sequenced in as little time as a single afternoon, at a laboratory cost of as little as $200.

The consequences of this feat are nothing short of revolutionary. Gene sequencing allows us to predict many hereditary diseases and the probability of getting cancer. This early benefit of gene sequencing became widely known when Angelina Jolie famously had a preventative double mastectomy after her personal genome sequencing indicated a high vulnerability to breast cancer. Genome sequencing helps scientists and doctors understand and develop treatments for scores of common and rare diseases. Along with advances in artificial intelligence, it helps determine medical treatments precisely tailored to the individual patient.

Longevity scientists have even identified a number of so-called longevity genes that can promise long and healthy lives to those who possess them. Scientists now understand far better than ever before the relationship between genes and aging. And while our genes do not significantly change from birth to death, our epigenomethe system of chemical modifications around our genes that determine how our genes are expresseddoes. The date on your birth certificate, it turns out, is but a single way to determine age. The biological age of your epigenome, many longevity scientists now believe, is far more important.

Best of all, however, science is beginning to offer ways to alter both your genome and epigenome for a healthier, longer life. New technologies like CRISPR-Cas9 and other gene-editing tools are empowering doctors with the extraordinary ability to actually insert, delete, or alter an individuals genes. In the not terribly distant future, we will be able to remove or suppress genes responsible for diseases and insert or amplify genes responsible for long life and health.

Gene editing is just one of the emerging technologies of the genetic revolution: Gene therapy works by effectively providing cells with genes that produce necessary proteins in patients whose own genes cannot produce them. This process is already being applied to a few rare diseases, but it will soon become a common and incredibly effective medical approach. The FDA expects to approve 10 to 20 such therapies by the year 2025.

Another major transformation driving the Longevity Revolution is the field of regenerative medicine. During aging, the bodys systems and tissues break down, as does the bodys ability to repair and replenish itself. For that reason, even those who live very long and healthy lives ultimately succumb to heart failure, immune system decline, muscle atrophy, and other degenerative conditions. In order to achieve our ambition of living to 200, we need a way to restore the body in the same way we repair a car or refurbish a home.

Several promising technologies are now pointing the way to doing just that. While it is still quite early, there are already a few FDA-approved stem cell therapies in the United States targeting very specific conditions. Stem cellscells whose job it is to generate all the cells, tissues, and organs of your bodygradually lose their ability to create new cells as we age. But new therapies, using patients own stem cells, are working to extend the bodys ability to regenerate itself. These therapies hold promise for preserving our vision, cardiac function, joint flexibility, and kidney and liver health; they can also be used to repair spinal injuries and help treat a range of conditions from diabetes to Alzheimers disease. The FDA has approved 10 stem cell treatments, with more likely on the way.

Its one thing to replenish or restore existing tissues and organs using stem cells, but how about growing entirely new organs? As futuristic as that sounds, it is already beginning to happen. Millions of people around the world who are waiting for a new heart, kidney, lung, pancreas, or liver will soon have their own replacement organs made to order through 3D bio-printing, internal bioreactors, or new methods of xenotransplantation, such as using collagen scaffoldings from pig lungs and hearts that are populated with the recipients own human cells.

Even if this generation of new biological organs fails, mechanical solutions will not. Modern bioengineering has successfully restored lost vision and hearing in humans using computer sensors and electrode arrays that send visual and auditory information directly to the brain. A prosthetic arm developed at Johns Hopkins is one of a number of mechanical limbs that not only closely replicate the strength and dexterity of a real arm but also can be controlled directly by the wearers mindjust by thinking about the desired movement. Today, mechanical exoskeletons allow paraplegics to run marathons, while artificial kidneys and mechanical hearts let those with organ failure live on for years beyond what was ever previously thought possible!

The third development underpinning the Longevity Revolution will look more familiar to most: connected devices. You are perhaps already familiar with common wearable health-monitoring devices like the Fitbit, Apple Watch, and ura Ring. These devices empower users to quickly obtain data on ones own health. At the moment, most of these insights are relatively trivial. But the world of small-scale health diagnostics is advancing rapidly. Very soon, wearable, portable, and embeddable devices will radically reduce premature death from diseases like cancer and cardiovascular disease, and in doing so, add years, if not decades, to global life expectancy.

[Photo: BenBella Books]The key to this part of the revolution is early diagnosis. Of the nearly 60 million lives lost around the globe each year, more than 30 million are attributed to conditions that are reversible if caught early. Most of those are noncommunicable diseases like coronary heart disease, stroke, and chronic obstructive pulmonary disease (bronchitis and emphysema). At the moment, once you have gone for your yearly physical exams, stopped smoking, started eating healthy, and refrained from having unprotected sex, avoiding life-threatening disease is a matter that is largely out of your hands. We live in a world of reactive medicine. Most people do not have advanced batteries of diagnostic tests unless theyre experiencing problems. And for a large percentage of the worlds population, who live in poor, rural, and remote areas with little to no access to diagnostic resources, early diagnosis of medical conditions simply isnt an option.

But not for long. Soon, healthcare will move from being reactive to being proactive. The key to this shift will be low-cost, ubiquitous, connected devices that constantly monitor your health. While some of these devices will remain external or wearable, others will be embedded under your skin, swallowed with your breakfast, or remain swimming through your bloodstream at all times. They will constantly monitor your heart rate, your respiration, your temperature, your skin secretions, the contents of your urine and feces, free-floating DNA in your blood that may indicate cancer or other disease, and even the organic contents of your breath. These devices will be connected to each other, to apps that you and your healthcare provider can monitor, and to massive global databases of health knowledge. Before any type of disease has a chance to take a foothold within your body, this armory of diagnostic devices will identify exactly what is going on and provide a precise, custom-made remedy that is ideal just for you.

As a result, the chance of your disease being diagnosed early will become radically unshackled from the limitations of cost, convenience, and medical knowledge. The condition of your body will be maintained as immaculately as a five-star hotel, and almost nobody will die prematurely of preventable disease.

There is one final seismic shift underpinning the Longevity Revolution, and its a real game-changer. Pouring forth from all of these digital diagnostic devices, together with conventional medical records and digitized research results, is a torrent of data so large it is hard for the human mind to even fathom it. This data will soon become grist for the mill of powerful artificial intelligence that will radically reshape every aspect of healthcare as we know it.

Take drug discovery, for instance. In the present day, it takes about 12 years and $2 billion to develop a new pharmaceutical. Researchers must painstakingly test various organic and chemical substances, in myriad combinations, to try to determine the material candidates that have the best chance of executing the desired medical effect. The drugs must be considered for the widest range of possible disease presentations, genetic makeup, and diets of targeted patients, side effects, and drug interactions. There are so many variables that it is little short of miraculous that our scientists have done so much in the field of pharmaceutical development on their own. But developing drugs and obtaining regulatory approval is a long and cash-intensive process. The result is expensive drugs that largely ignore rarer conditions.

AI and data change that reality. Computer models now look at massive databases of patient genes, symptoms, disease species, and millions of eligible compounds to quickly determine which material candidates have the greatest chance of success, for which conditions, and according to what dose and administration. In addition to major investments by Big Pharma, there are currently hundreds of startups working to implement the use of AI to radically reshape drug discovery, just as we saw happen in the race to develop COVID-19 vaccines. The impact that this use of AI and data will have on treating or even eliminating life-threatening diseases cannot be overstated.

But that is not the only way that artificial intelligence is set to disrupt healthcare and help set the Longevity Revolution in motion. It will also form the foundation of precision medicinethe practice of custom-tailoring health treatments to the specific, personal characteristics of the individual.

Today, healthcare largely follows a one-size-fits-all practice. But each of us has a very unique set of personal characteristics, including our genes, microbiome, blood type, age, gender, size, and so on. AI will soon be able to access and analyze enormous aggregations of patient data pulled together from medical records, personal diagnostic devices, research studies, and other sources to deliver highly accurate predictions, diagnoses, and treatments, custom-tailored to the individual. As a result, healthcare will increasingly penetrate remote areas, becoming accessible to billions of people who today lack adequate access to medical care.

I predict that the development of AI in healthcare will change how we live longer, healthier lives as radically as the introduction of personal computers and the internet changed how we work, shop, and interact. Artificial intelligence will eliminate misdiagnosis; detect cancer, blood disease, diabetes, and other killers as early as possible; radically accelerate researchers understanding of aging and disease; and reestablish doctors as holistic care providers who actually have time for their patients. In as little as 10 years time, we will look back at the treatment of aging and disease today as quite naive.

The Longevity Revolution lives not in the realm of science fiction but in the reality of academic research laboratories and commercial technology R&D centers. The idea of aging as a fixed and immutable quality of life that we have no influence upon is ready to be tossed into the dustbin of history.

Sergey Young is a renowned VC, longevity visionary, and founder of the $100 million Longevity Vision Fund. This is an adapted excerpt from The Science and Technology of Growing Young, with permission by BenBella Books.

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These 4 tech breakthroughs could help end aging - Fast Company

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Human Embryonic Stem Cells (HESC) Market Updates to 2021: Brief, Trends, Applications, Types, Research, Forecast to 2028 UNLV The Rebel Yell – UNLV…

Monday, August 30th, 2021

The global Human Embryonic Stem Cells (HESC) Market has been comprehensively analyzed and the results are presented in the market report published. The market concentration that is currently occupied by the Human Embryonic Stem Cells (HESC) market and an overview of the Human Embryonic Stem Cells (HESC) manufacturing industry is extensively researched in the report. An analysis of the collected data is used to reveal the market revenue earned by the different companies operating in the Human Embryonic Stem Cells (HESC) industry.

The global Human Embryonic Stem Cells (HESC) market depends on different factors that can either be a positive influence on the global market or cause the market to decline. The factors are identified and are categorized based on the effect that they can have on the market. The various factors are identified across all market segments and the different regions that are mentioned in the report.

Get Free Sample PDF (including COVID19 Impact Analysis, full TOC, Tables and Figures): About Us: https://www.datalibraryresearch.com/sample-request/human-embryonic-stem-cells-hesc-market-2728?utm_source=unlvrebelyell&utm_medium=41

The objective of the study is to define market sizes of different segments and countries in previous years and to forecast the values to the next Five years. The report is designed to incorporate both qualify qualitative and quantitative aspects of the industry with respect to each of the regions and countries involved in the study. Furthermore, the report also caters the detailed information about the crucial aspects such as drivers and restraining factors which will define the future growth of the Human Embryonic Stem Cells (HESC) market.

Some of The Companies Competing in The Human Embryonic Stem Cells (HESC) Market are Astellas Institute of Regenerative Medicine, Asterias Biotherapeutics Inc., BD Biosciences, Cell Cure Neurosciences Ltd. (Israel),Cellular Dynamics International,GE Healthcare (UK), MilliporeSigma, PerkinElmer Inc., Reliance Life Sciences Ltd. (India),Research and Diagnostics Systems Inc., SABiosciences Corp.

It takes into account the CAGR, value, volume, revenue, production, consumption, sales, manufacturing cost, prices, and other key factors related to the global Human Embryonic Stem Cells (HESC) market. All findings and data on the global Human Embryonic Stem Cells (HESC) market provided in the report are calculated, gathered, and verified using advanced and reliable primary and secondary research sources. The regional analysis offered in the report will help you to identify key opportunities of the global Human Embryonic Stem Cells (HESC) market available in different regions and countries.

Market Analysis, Insights and Forecast By Type

Totipotent Stem Cell Pluripotent Stem Cell Unipotent Stem Cell

Market Analysis, Insights and Forecast By Application

Regenerative medicine Stem cell biology research Tissue engineering Toxicology testing

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The study objectives of this report are:

To study and analyze the global Human Embryonic Stem Cells (HESC) consumption (value & volume) by key regions/countries, product type and application, history data from 2014 to 2018, and forecast to 2028.

To understand the structure of Human Embryonic Stem Cells (HESC) market by identifying its various subsegments.

Focuses on the key global Human Embryonic Stem Cells (HESC) manufacturers, to define, describe and analyze the sales volume, value, market share, market competition landscape, SWOT analysis and development plans in next few years.

To analyze the Human Embryonic Stem Cells (HESC) with respect to individual growth trends, future prospects, and their contribution to the total market.

To share detailed information about the key factors influencing the growth of the market (growth potential, opportunities, drivers, industry-specific challenges and risks).

To project the consumption of Human Embryonic Stem Cells (HESC) submarkets, with respect to key regions (along with their respective key countries).

To analyze competitive developments such as expansions, agreements, new product launches, and acquisitions in the market.

To strategically profile the key players and comprehensively analyze their growth strategies.

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Go here to read the rest:
Human Embryonic Stem Cells (HESC) Market Updates to 2021: Brief, Trends, Applications, Types, Research, Forecast to 2028 UNLV The Rebel Yell - UNLV...

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