StemCell Therapy

Cell potency is a cell's ability to differentiate into other cell types[1][2][3] The more cell types a cell can differentiate into, the greater its potency. Potency is also described as the gene activation potential within a cell which like a continuum begins with totipotency to designate a cell with the most differentiation potential, pluripotency, multipotency, oligopotency and finally unipotency.

Totipotency (Lat. totipotentia, "ability for all [things]") is the ability of a single cell to divide and produce all of the differentiated cells in an organism. Spores and zygotes are examples of totipotent cells.[4] In the spectrum of cell potency, totipotency is a form of pluripotency that represents the cell with the greatest differentiation potential.

It is possible for a fully differentiated cell to return to a state of totipotency.[5] This conversion to totipotency is complex, not fully understood and the subject of recent research. Research in 2011 has shown that cells may differentiate not into a fully totipotent cell, but instead into a "complex cellular variation" of totipotency.[6] Stem cells resembling totipotent blastomeres from 2-cell stage embryos can arise spontaneously in mouse embryonic stem cell cultures[7][8] and also can be induced to arise more frequently in vitro through down-regulation of the chromatin assembly activity of CAF-1.[9]

The human development model is one which can be used to describe how totipotent cells arise.[10] Human development begins when a sperm fertilizes an egg and the resulting fertilized egg creates a single totipotent cell, a zygote.[11] In the first hours after fertilization, this zygote divides into identical totipotent cells, which can later develop into any of the three germ layers of a human (endoderm, mesoderm, or ectoderm), or into cells of the placenta (cytotrophoblast or syncytiotrophoblast). After reaching a 16-cell stage, the totipotent cells of the morula differentiate into cells that will eventually become either the blastocyst's Inner cell mass or the outer trophoblasts. Approximately four days after fertilization and after several cycles of cell division, these totipotent cells begin to specialize. The inner cell mass, the source of embryonic stem cells, becomes pluripotent.

Research on Caenorhabditis elegans suggests that multiple mechanisms including RNA regulation may play a role in maintaining totipotency at different stages of development in some species.[12] Work with zebrafish and mammals suggest a further interplay between miRNA and RNA-binding proteins (RBPs) in determining development differences.[13]

In cell biology, pluripotency (Lat. pluripotentia, "ability for many [things]")[14] refers to a stem cell that has the potential to differentiate into any of the three germ layers: endoderm (interior stomach lining, gastrointestinal tract, the lungs), mesoderm (muscle, bone, blood, urogenital), or ectoderm (epidermal tissues and nervous system).[15] However, cell pluripotency is a continuum, ranging from the completely pluripotent (or totipotent) cell that can form every cell of the embryo proper, e.g., embryonic stem cells and iPSCs (see below), to the incompletely or partially pluripotent cell that can form cells of all three germ layers but that may not exhibit all the characteristics of completely pluripotent cells.

Induced pluripotent stem cells, commonly abbreviated as iPS cells or iPSCs, are a type of pluripotent stem cell artificially derived from a non-pluripotent cell, typically an adult somatic cell, by inducing a "forced" expression of certain genes and transcription factors.[16] These transcription factors play a key role in determining the state of these cells and also highlights the fact that these somatic cells do preserve the same genetic information as early embryonic cells.[17] The ability to induce cells into a pluripotent state was initially pioneered in 2006 using mouse fibroblasts and four transcription factors, Oct4, Sox2, Klf4 and c-Myc;[18] this technique, called reprogramming, earned Shinya Yamanaka and John Gurdon the Nobel Prize in Physiology or Medicine 2012.[19] This was then followed in 2007 by the successful induction of human iPSCs derived from human dermal fibroblasts using methods similar to those used for the induction of mouse cells.[20] These induced cells exhibit similar traits to those of embryonic stem cells (ESCs) but do not require the use of embryos. Some of the similarities between ESCs and iPSCs include pluripotency, morphology, self-renewal ability, a trait that implies that they can divide and replicate indefinitely, and gene expression.[21]

Epigenetic factors are also thought to be involved in the actual reprogramming of somatic cells in order to induce pluripotency. It has been theorized that certain epigenetic factors might actually work to clear the original somatic epigenetic marks in order to acquire the new epigenetic marks that are part of achieving a pluripotent state. Chromatin is also reorganized in iPSCs and becomes like that found in ESCs in that it is less condensed and therefore more accessible. Euchromatin modifications are also common which is also consistent with the state of euchromatin found in ESCs.[21]

Due to their great similarity to ESCs, iPSCs have been of great interest to the medical and research community. iPSCs could potentially have the same therapeutic implications and applications as ESCs but without the controversial use of embryos in the process, a topic of great bioethical debate. In fact, the induced pluripotency of somatic cells into undifferentiated iPS cells was originally hailed as the end of the controversial use of embryonic stem cells. However, iPSCs were found to be potentially tumorigenic, and, despite advances,[16] were never approved for clinical stage research in the United States. Setbacks such as low replication rates and early senescence have also been encountered when making iPSCs,[22] hindering their use as ESCs replacements.

Additionally, it has been determined that the somatic expression of combined transcription factors can directly induce other defined somatic cell fates (transdifferentiation); researchers identified three neural-lineage-specific transcription factors that could directly convert mouse fibroblasts (skin cells) into fully functional neurons.[23] This result challenges the terminal nature of cellular differentiation and the integrity of lineage commitment; and implies that with the proper tools, all cells are totipotent and may form all kinds of tissue.

Some of the possible medical and therapeutic uses for iPSCs derived from patients include their use in cell and tissue transplants without the risk of rejection that is commonly encountered. iPSCs can potentially replace animal models unsuitable as well as in vitro models used for disease research.[24]

Recent findings with respect to epiblasts before and after implantation have produced proposals for classifying pluripotency into two distinct phases: "naive" and "primed".[25] The baseline stem cells commonly used in science that are referred as Embryonic stem cells (ESCs) are derived from a pre-implantation epiblast; such epiblast is able to generate the entire fetus, and one epiblast cell is able to contribute to all cell lineages if injected into another blastocyst. On the other hand, several marked differences can be observed between the pre- and post-implantation epiblasts, such as their difference in morphology, in which the epiblast after implantation changes its morphology into a cup-like shape called the "egg cylinder" as well as chromosomal alteration in which one of the X-chromosomes undergoes random inactivation in the early stage of the egg cylinder, known as X-inactivation.[26] During this development, the egg cylinder epiblast cells are systematically targeted by Fibroblast growth factors, Wnt signaling, and other inductive factors via the surrounding yolk sac and the trophoblast tissue,[27] such that they become instructively specific according to the spatial organization.[28] Another major difference that was observed, with respect to cell potency, is that post-implantation epiblast stem cells are unable to contribute to blastocyst chimeras,[29] which distinguishes them from other known pluripotent stem cells. Cell lines derived from such post-implantation epiblasts are referred to as epiblast-derived stem cells which were first derived in laboratory in 2007; despite their nomenclature, that both ESCs and EpiSCs are derived from epiblasts, just at difference phases of development, and that pluripotency is still intact in the post-implantation epiblast, as demonstrated by the conserved expression of Nanog, Fut4, and Oct-4 in EpiSCs,[30] until somitogenesis and can be reversed midway through induced expression of Oct-4.[31]

Multipotency describes progenitor cells which have the gene activation potential to differentiate into discrete cell types. For example, a multipotent blood stem cell and this cell type can differentiate itself into several types of blood cell types like lymphocytes, monocytes, neutrophils, etc., but it is still ambiguous whether HSC possess the ability to differente into brain cells, bone cells or other non-blood cell types.[citation needed]

New research related to multipotent cells suggests that multipotent cells may be capable of conversion into unrelated cell types. In another case, human umbilical cord blood stem cells were converted into human neurons.[32] Research is also focusing on converting multipotent cells into pluripotent cells.[33]

Multipotent cells are found in many, but not all human cell types. Multipotent cells have been found in cord blood,[34] adipose tissue,[35] cardiac cells,[36] bone marrow, and mesenchymal stem cells (MSCs) which are found in the third molar.[37]

MSCs may prove to be a valuable source for stem cells from molars at 810 years of age, before adult dental calcification. MSCs can differentiate into osteoblasts, chondrocytes, and adipocytes.[38]

In biology, oligopotency is the ability of progenitor cells to differentiate into a few cell types. It is a degree of potency. Examples of oligopotent stem cells are the lymphoid or myeloid stem cells.[2] A lymphoid cell specifically, can give rise to various blood cells such as B and T cells, however, not to a different blood cell type like a red blood cell.[39] Examples of progenitor cells are vascular stem cells that have the capacity to become both endothelial or smooth muscle cells.

In cell biology, a unipotent cell is the concept that one stem cell has the capacity to differentiate into only one cell type. It is currently unclear if true unipotent stem cells exist. Hepatoblasts, which differentiate into hepatocytes (which constitute most of the liver) or cholangiocytes (epithelial cells of the bile duct), are bipotent.[40] A close synonym for unipotent cell is precursor cell.

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Cell potency - Wikipedia

MERIDA The Faculty of Dentistry of the Autonomous University of Yucatan (UADY, for its acronym in Spanish) has inaugurated its Translational Cell Laboratory, the only one of its kind in the southeast of the country, where research will be carried out with cells of dental origin in which rodents will be used in order to regenerate bones.

The head of the new laboratory, Ricardo Pealoza Cuevas, explained in an interview with Notimex that the research will consist of taking samples from the mouth of a human, such as a tooth or a molar, which inside have the dental pulp, which can be used in the reproduction of cells with multiple tissues.

Among the dental pieces that can be used for these processes are the premolars or third molars, known as wisdom teeth, and even the milkteeth that are lost in the early years of childhood, he said.

Laboratory at UADY. (PHOTO: Seeding Labs)

He commented that stem cells could replace the embryonic ones, and in this way future studies would investigate the cure for the prevention of degenerative or chronic diseases as in the case of Parkinson or Alzheimer.

It is already being investigated for the treatment of diabetes, which is one of the major diseases in Yucatan, added Pealoza Cuevas.

He noted that the membranes of stem cells of dental origin allow the regeneration of bones or other tissues, as well as treatments for other diseases already mentioned.

In this research students will play an important role, putting into practice the knowledge acquired in the classroom.

This laboratory is a real learning scenario where students develop their skills as set by their Educational Model for Integral Training (MEFI, for its acronym in Spanish), but above all their social responsibility, as a hallmark in their future professional performance, added the academic.

The specialists will initiate the research at the International Symposium of Stem Cells and VII Theoretical-Practical Course Cells of Pulp Origin, that is carried out from August 28 to September 2 in the Faculty of Dentistry.

In an interdisciplinary effort between the Faculties of Dentistry and Chemical Engineering of UADY, the objective is to promote these lines of research, whose progress will be presented throughout the symposium.

Source:http://www.notimex.gob.mx/

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University of Yucatan launches stem cell laboratory - The Yucatan ... - The Yucatan Times

In his office at the University of Pennsylvania, oral and maxillofacial surgeon Rabie Shanti sits at his computer, clicking through photos of patients hes operated on.

He pulls up an image of a mouth open wide, tongue extended.

This is a recent case, he says, pointing to one side of the tongue that looks slightly different from the other. This is forearm skin with an artery and vein taken from the arm. That surgery was done the same day the patient had their tongue cancer resected. We used those tissues and vessels to reconstruct the tongue to allow this patient to maintain their ability to eat and speak after having almost half of their tongue removed.

Those familiar with grafting surgery may understand that, after a burn, for example, surgeons can take portions of skin from one part of the body to replace skin lost from another area. But what Shanti is describing is something even more mind-bending. He reconstructs tongues, as well as other portions of the oral cavity, using tissues and bone harvested from other parts of the patients own body.

The work is remarkable, but taxing for the patient. So when hes not busy in the clinic, Shanti, who joined Penns School of Dental Medicine as an assistant professor last year, is devoting energy in the lab to better understand what drives oral cancers and to design new structures that will more effectively replace the tissues his patients lose during surgery, whether due to cancerous or benign tumors, trauma or inflammatory conditions.

I think that I was always fascinated with the idea of putting something back together, says Shanti, who also holds an appointment as assistant professor in Penns Perelman School of Medicine. Most of what is done in dentistry is really reconstructive, whether its rebuilding the tooth surface or part of the jaw.

When Shanti was a college student at Florida Atlantic University, he became interested in pursuing dental medicine as a career, though being a surgeon was not on his radar.

At that time, aside from having braces, I had no deep experience with dentistry, he says. I thought I wanted to be an orthodontist. I didnt know what an oral and maxillofacial surgeon was until I was in dental school.

He attended dental school at Harvard University, pausing his studies to spend two years as a Howard Hughes Medical Institute research scholar working in an orthopedics laboratory at the National Institutes of Healths National Institute for Arthritis and Musculoskeletal and Skin Diseases. The lab was headed by Rocky Tuan, who is now at the University of Pittsburgh. At the NIAMS, Shanti delved into tissue engineering, focusing on designing new materials to help regrow muscle and bone.

I quickly noticed that my research interests were fueled by my clinical interests, and one area that really interested me was reconstructive surgery of the jaw and tongue, particularly reconstruction for pathology, he says. Seeing someone who had a benign tumor or cancer that involved their upper or lower jaw bone, and now theyve lost that part of their body, but being able to make someone whole again, that really drew me in.

After completing his dental degree, Shanti went on to pursue his residency in oral and maxillofacial surgery at Rutgers University, an experience he likens to being a kid in a candy store, enticed by all the possible areas in which to focus. He earned his M.D. at Rutgers along the way. He then went on to Louisiana State University for a two-year fellowship, pursuing research and bolstering his experience in reconstructive microsurgery, which involves taking tissues and blood vessels from one part of the body and connecting them to another part of the body to make it a living tissue. Shanti left LSU for Penn in 2016.

Through much of his training and still today, Shanti has pursued research in an area that sparked his interest early on in dental school: ameloblastoma, a rare tumor of the jaw, affecting 1 in 2 million people. This tumor type is resistant to most forms of treatment, leaving patients with surgery as the only viable option. These procedures often result in the loss of large portions of the lower or upper jaw.

Shantis investigations have examined the role of mesenchymal stem cells, which dwell in the bone marrow, in supporting ameloblastoma tumors. Working with his research mentor, Anh Le, the Norman Vine Endowed Professor of Oral Rehabilitation and chair of the Department of Oral and Maxillofacial Surgery/Pharmacology at Penn Dental Medicine, Shanti has looked for ways to disrupt the communication between these stem cells and tumor cells as a way of possible preventing their aggressive growth.

A second research interest for Shanti is tissue engineering, specifically to improve tongue reconstructions. The tongue can be affected by invasive squamous cell carcinoma, and to treat it can involve removing large portions of tissue. Shanti works closely with Le in her lab at Penn Dental Medicine towardengineering constructs that could help a patient regrow tissue rather than using tissue taken from another body part.

I think were on the cusp with tissue engineering and using engineered stem-cell-based constructs to reconstruct tissues of the head and neck, says Shanti. I think thats going to be a really significant advancement in reconstructive surgery that I hope to be a part of during my career and lifetime.

In the clinic, Shanti alternates time seeing patients at the Hospital of the University Pennsylvania and Pennsylvania Hospital, working with colleagues to address the diverse needs of his patients. He notes that the comprehensive and collaborative care offered by Penn was part of the appeal of joining the faculty here.

For patients with head and neck cancer, the part of the body that is affected, our face and head, is not only part of our identity, but it has significant functions, Shanti says. Penns Abramson Cancer Center, of which the faculty of Penn Dentals Department of Oral and Maxillofacial Surgery are part, brings all the specialists together to get these patients back to their day-to-day. Our team includes surgeons, radiation oncologists, medical oncologists, nurse navigators, speech language pathologists, nutritionists, social workers, oral-medicine specialists, prosthodontists, and we all go over each case together. Its patient-centered rather than practitioner-centered.

Shanti has seen a lot of progress in his field. Today, hes able to plan out surgeries thoroughly in advance using digital tools.

I can get on a computer with images of the patient, design the surgery, simulate it and identify where Im going to make the cuts in bone, how the tumor is going to come out and how Im going to rebuild it, he says. Then Im provided with customized materials, cutting guides and plates designed specifically for the patient. It not only helps increase the precision and accuracy of the surgery, but it also minimizes the time we spend in the operating room because were not doing that guess work thats already done.

Still he feels there is a long way to go.

Describing another case, Shanti this time shows a photo of a bright, healthy-looking smile.

This is from a patient I saw Monday, he says. She had an ameloblastoma and we did a computer planned and customized free-flap reconstruction using bone and skin from her lower leg. She has a dental prosthesis and is doing well.

Shanti hopes it wont be long before many more patients will be able to arrive at this stage, with fewer invasive procedures.

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Penn Oral and Maxillofacial Surgeon Driven by Desire to 'Make Someone Whole Again' - Penn Current

Dr Maos team have found a way of building a scaffold for a tooth made of stem cells stimulating the growth of a new tooth using DNA. The new tooth grows over this template in nine weeks.

Dr Mao pioneered this technique at Columbia Universitys Tissue Engineering and Regenerative Medicine Laboratory. First, a 3D scaffold is composed; then, it is implanted in the mouth. In the nine weeks after implantation, stem cells migrate to the scaffold and initiate the growth of new dental tissue.

The missing tooth is replaced with stem cells from your body, and the tooth starts merging to the surrounding tissue on its own. This boosts the regeneration process and results in regrowth of the tooth in a record time, Dr Mao explains.

A human molar scaffold.

This method makes the most of stem cell research that has been gaining momentum in recent years. Stem cell research is being used to treat everything from broken bones to genetic disorders.

The procedure is still in the research stage and is not available to the public yet, but it should make it into dental surgeries in the not so distant future.

This discovery helps the body regrow teeth in the mouth on its own. It could mean the end of expensive dental surgery to replace missing or broken teeth.

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Healthy Friday: In the not so distant future we will be able to grow ... - Krugersdorp News

Natalya Pshibytko

MINSK, 30 August (BelTA) Transplants based on stem cells have been developed for dentistry and ophthalmology in Belarus, BelTA learned from Natalya Pshibytko, Deputy Director for Science and Innovations of the Biophysics and Cell Engineering Institute of the National Academy of Sciences of Belarus (NASB).

Natalya Pshibytko said: As far as dentistry is concerned, together with medics and the Belarusian Medical Academy of Post-Graduate Education we are developing a technology for treating periodontium diseases. We have created a transplant based on mesenchymal stem cells and various 2D and 3D carriers, which will help treat such diseases. Clinical trials are nearing completion. There are plans to start adopting these methods next year. As for ophthalmology, for treating cornea ailments a bio transplant has been created based on mesenchymal stem cells of the fat tissue of the eye and based on limbal stem cells. The transplant is going through clinical trials, too.

The Biophysics and Cell Engineering Institute also offers treatment of trophic ulcers using stem technologies. Patients, who have been suffering for decades, come to us. Dozens of patients have been cured already using our method. In every case we saw a lasting positive effect, with wounds healing and pain going away, noted the official.

The institute's R&D products are also used in agriculture. A facility to develop and manufacture a feed supplement based on chlorella suspension has been established. This water plant is rich in vitamins, antioxidants, and proteins. Trials indicate that the feed supplement improve chicken egg production and the survival rate of young animals. We are now working to create a substitute for imported feed for sturgeons, added Natalya Pshibytko.

Work to create a facility to manufacture spirulina water plant began last year. The plant is rich in vitamins, antioxidants, and nutrients, this is why it is primarily used as a feed supplement. But scientists also bear in mind pharmaceutical applications since spirulina is used to make chlorin E6 for the Fotolon medication.

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Belarusian scientists come up with transplants based on stem cells ... - Belarus News (BelTA)

Dr Maos team have found a way of building a scaffold for a tooth made of stem cells stimulating the growth of a new tooth using DNA. The new tooth grows over this template in nine weeks.

Dr Mao pioneered this technique at Columbia Universitys Tissue Engineering and Regenerative Medicine Laboratory. First, a 3D scaffold is composed; then, it is implanted in the mouth. In the nine weeks after implantation, stem cells migrate to the scaffold and initiate the growth of new dental tissue.

The missing tooth is replaced with stem cells from your body, and the tooth starts merging to the surrounding tissue on its own. This boosts the regeneration process and results in regrowth of the tooth in a record time, Dr Mao explains.

A human molar scaffold.

This method makes the most of stem cell research that has been gaining momentum in recent years. Stem cell research is being used to treat everything from broken bones to genetic disorders.

The procedure is still in the research stage and is not available to the public yet, but it should make it into dental surgeries in the not so distant future.

This discovery helps the body regrow teeth in the mouth on its own. It could mean the end of expensive dental surgery to replace missing or broken teeth.

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Healthy Friday: In the not so distant future we will be able to grow new teeth - Pretoria Moot Rekord

Bone marrow contains hematopoetic stem cells, the precursors to every blood cell type. These cells spring into action following bone marrow transplants, bone marrow injury and during systemic infection, creating new blood cells, including immune cells, in a process known as hematopoiesis.

A new study led by University of Pennsylvania and Technical University of Dresden scientists has identified an important regulator of this process, a protein called Del-1. Targeting it, the researchers noted, could be an effective way to improve stem cell transplants for both donors and recipients. There may also be ways to modulate levels of Del-1 in patients with certain blood cancers to enhance immune cell production. The findings are reported this week in The Journal of Clinical Investigation.

Because the hematopoetic stem cell niche is so important for the creation of bone marrow and blood cells and because Del-1 is a soluble protein and is easily manipulated, one can see that it could be a target in many potential applications, said George Hajishengallis, the Thomas W. Evans Centennial Professor in the Department of Microbiology in Penns School of Dental Medicine and a senior author on the work.

I think that Del-1 represents a major regulator of the hematopoetic stem cell niche, said Triantafyllos Chavakis, co-senior author on the study and a professor at the Technical University of Dresden. It will be worthwhile to study its expression in the context of hematopoetic malignancy.

For Hajishengallis, the route to studying Del-1 in the bone marrow began in his field of dental medicine. Working with Chavakis, he had identified Del-1 as a potential drug target for gum disease after finding that it prevents inflammatory cells from moving into the gums.

Both scientists and their labs had discovered that Del-1 was also expressed in the bone marrow and began following up to see what its function was there.

In the beginning, I thought it would have a simple function, like regulating the exit of mature leukocytes [white blood cells] from the marrow into the periphery, Hajishengallis said, something analogous to what it was doing in the gingiva. But it turned out it had a much more important and global role than what I had imagined.

The researchers investigations revealed that Del-1 was expressed by at least three cell types in the bone marrow that support hematopoetic stem cells: endothelial cells, CAR cells and osteoblasts. Using mice deficient in Del-1, they found that the protein promotes proliferation and differentiation of hematopoetic stem cells, sending more of these progenitor cells down a path toward becoming myeloid cells, such as macrophages and neutrophils, rather than lymphocytes, such as T cells and B cells.

In bone marrow transplant experiments, the team discovered that the presence of Del-1 in recipient bone marrow is required for the transplanted stem cells to engraft in the recipient and to facilitate the process of myelopoesis, the production of myeloid cells.

When the researchers mimicked a systemic infection in mice, animals deficient in Del-1 were slower to begin making myeloid cells again compared to those with normal Del-1 levels.

We saw roles for Del-1 in both steady state and emergency conditions, Hajishengallis said.

Hajishengallis, Chavakis and their colleagues identified the protein on hematopoetic stem cells with which Del-1 interacts, the 3 integrin, perhaps pointing to a target for therapeutic interventions down the line.

The scientists see potential applications in bone marrow and stem cell transplants, for both donors and recipients. In donors, blocking the interaction between Del-1 and hematopoetic stem cells could enhance the mobilization of those progenitors into the bloodstream. This could be helpful for increasing donor cell numbers for transplantation. Transplant recipients, on the other hand, may need enhanced Del-1 interaction to ensure the transplanted cells engraft and begin making new blood cells more rapidly.

In addition, people undergoing chemotherapy who develop febrile neutropenia, associated with low levels of white blood cells, might benefit from the role of Del-1 in supporting the production of immune-related blood cells such as neutrophils.

Its easy to think of practical applications for these findings, said Hajishengallis. Now we need to find out whether it works in practice, so our studies continue.

Ioannis Mitroulis, Lan-Sun Chen and Rashim Pal Singh of TU-Dresden were co-lead authors on the study, and Ben Wielockx of TU-Dresden was a co-senior author along with Hajishengallis and Chavakis. They were joined by coauthors Tetsuhiro Kajikawa, Kavita Hosur, Tomoki Maekawa and Baomei Wang of Penn Dental Medicine; Ioannis Kourtzelis, Matina Economopoulou, Maria Troullinaki, Athanasios Ziogas, Klara Ruppova, Pallavi Subramanian, Panayotis Verginis, Malte Wobus, Martin Bornhuser and Tatyana Grinenko of TU-Dresden; Torsten Tonn of the German Red Cross Blood Donation Service in Dresden; and Marianna Di Scala and Andrs Hidalgo of the Spanish National Center for Cardiovascular Research.

The study was supported by the Deutsche Forschungsgemeinschaft, European Commission, European Research Council and National Institutes of Health (grants AI068730, DE024153, DE024716, DE0152 54 and DE026152).

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Bone Marrow Protein May Be Target for Improving Stem Cell Transplants - Penn: Office of University Communications

A new University of Michigan study found the combination of traditional chemotherapy drug, cisplatin, with an experimental drug destroys a rare type of salivary gland tumor and prevents it from reoccurring within 300 days after treatment. The study was conducted on mice as well as primary human adenoid cystic carcinoma cells in the Nr Lab at the School of Dentistry.

The salivary gland tumor is a product of ACC, which is a rare cancer of the salivary glands and of surrounding head and neck areas. The cancer typically arises in adulthood and affects about 3,000 to 4,000 people per year. Treatment of advanced ACC with traditional chemotherapy has only had limited success.

LSA sophomore Leo Thompson, a pre-dental student, found the results to be inspiring for the future of ACC cancer care. As someone looking forward to attending dental school, Thompson was very interested in the studys results.

The study gives a promising outlook towards defeating ACC, Thompson said. Hopefully the prevention of recurrence can be achieved in the long term, and we see the treatment curing humans in a few years.

ACC is known to grow slowly; however, it is often discovered in the late, aggressive stages. There is no cure for the cancer, and the tumor cells have a tendency to reappear later at their original site. This is a serious concern for physicians treating ACC patients. The cancer tends to spread to other parts of the body, especially the lungs, leading to additional life-threatening issues.

The study found mice treated with the experimental drug, MI-773, combined with cisplatin had shrunken tumors, ranging from being the size of an acorn to being nonexistent. Next, the acorn-sized tumors were removed from the mice and subjects continued to take MI-773 for another month. This treatment group eradicated tumor recurrences for more than 300 days.

On the other hand, 62.5 percent of control mice that only received surgical removal of the tumor saw recurrences. These results suggest this combination treatment may be more effective in treating human patients with ACC.

LSA senior Samantha Sciancalepore, a pre-dental student, said she was eager to see what the future holds for this kind of research.

I think its really (admirable) that this research is being done on our campus, she said. I feel lucky that we have the tools to research solutions to cancer, especially in facial tumors. As a dentist, I think one of your ultimate goals is to provide help and comfort to your patients, and I think this sort of conclusive research is exactly what they need to advance.

Most cancers attempt to block the cancer-fighting protein p53 so the protein can no longer kill the cancer. However, this is not the case with ACC tumors, which tend to leave p53 untouched. This makes MI-773 suitable for treating ACC, which works by preventing the tumor from attacking p53.

Primary investigator Jacques Nr, professor of dentistry, otolaryngology and biomedical engineering, explained in an interview with Michigan News the importance of MI-773 in staving off the cancer. MI-773 stops the interaction between cancer cells and p53, which might otherwise be fatal for the patient.

This drug MI-773 prevents that interaction, so p53 can induce cell death, Nr said. In this study, when researchers activated p53 in mice with salivary gland cancer, the cancer stem cells died.

MI-773 was discovered by study co-author Shaomeng Wang, professor of medicine, pharmacology and medical chemistry. The drug is licensed to Sanofi, a French pharmaceutical company known to engage in the research and development aspects of medicine.

A major drawback of the study is that it was conducted over a 300-day period, whereas studies show ACC tumors tend to reappear after 10 years.

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Dentistry school uncovers new treatment for gland cancer - The Michigan Daily

The global market for stem cells has been estimated at USD 12 billion in 2016and is projected to reach USD 26.6 billion by 2021, at a CAGR of 13.7% during the forecast period 2016to 2021. A stem cell is an undifferentiated cell that has the potential to develop into any type of cell in the body.

Regenerative medicine is the major application of stem cells and other areas are neurology, orthopedics, oncology, cardiology, hematology and others (diabetes, injuries, and wounds). Another prominent application of stem cells is drug discovery and development. The end-users of this market are usually hospitals, cell banks, clinical research laboratories and academic institutes.

Global Stem Cell Marketing Market Dynamics

The global stem cells market is one of the most promising markets in the field of life sciences at present and is forecasted to grow even more in the coming years as stem cells enable cost-effective treatment of many conditions that currently have poor or no treatment.

Drivers

Some of the factors driving the global stem cells market are:

Restraints

While the global stem cells market has ample scope for growth, there are some factors restraining it as well. These include:

The market for stem cells is segmented on the basis of cell types and technology. The cells type segment includes adult stem cells, human embryonic stem cells, induced pluripotent stem cells, rat neural stem cells and very small embryonic-like stem cells. Adult stem cells are again divided into hematopoietic stem cells, mesenchymal stem cells, neuronal stem cells, dental stem cells and umbilical cord cells. The adult stem cells hold the highest share in the global stem cells market, while the market share of induced pluripotent stem cells is expected to grow in the coming years. The technology segment is divided into stem cell acquisition, stem cell production, stem cell cryopreservation, and stem cell expansion sub-segments.

Based on geography, the global market for stem cells is segmented into North America, Europe, Asia-Pacific and Rest of the World. The global stem cells market is dominated byNorth America, followed byEurope, the estimated market share of which is more than 25% as per a recent study. With 30% of the market, the USA holds the majority of share. However, due to increasing awareness among the public and advances in technologies, the market in the Asia-Pacific is expected to grow at a high rate.

Many players in this market are trying to expand their product portfolio in order to top the global market. While some companies are entering into the market by acquisitions, top companies are expanding their growth in this market by acquiring other companies. Few companies have adopted product innovation and new product launches as their key business strategy to ensure their dominance in this market.

Some of the key players in the market are:

Key Deliverables in the Study

If you are in need of BioTechnology marketing or Stem Cell Marketing call 972-800-6670

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BioTech Marketing and market opportunity for Stem Cells - Checkbiotech.org (press release)

Stem cells are the highly versatile spare tires of your body. Once called on, they can replace a damaged cell and, because they aren't yet directed to become part of a specific organ or tissue type, they not only could become (metaphorically speaking) a new tire, but could also fix a worn-out engine part or a cracked windshield. It just takes the right prodding in the body, or the laboratory! They can do it even after being inactive for a long time.

Those remarkable abilities are promising to provide scientists with a powerful tool to use in conquering disease. That's because normally, cells in organs such as the heart and pancreas do not divide to repair damage that might happen to the organ. But manipulation of stem cells ... well, that could allow doctors to induce self-repair in many parts of the body. No more heart transplants; bye, bye diabetes, macular degeneration, spinal cord injury, osteo- and rheumatoid arthritis. We might even repair third-degree burns and stroke damage that was previously considered permanent.

That promising future became more hopeful in 2006, when researchers figured out how to turn specialized adult stem cells (replacing use of embryonic cells in some research) into what they called "induced pluripotent stem cells" (iPSCs). Since then, the number of experiments using iPSCs has sky-rocketed: Adult mouse stem cells are injected into the damaged ventricular wall of a mouse heart and the stem cells regenerated damaged heart muscle! There have been a few, small, human-based studies that, says the National Institutes of Health, have "demonstrated that stem cells that are injected into the circulation or directly into the injured heart tissue appear to improve cardiac function and/or induce the formation of new capillaries." But and this is a big but they caution, "significant technical hurdles remain that will only be overcome through years of intensive research."

Tip: Stem cell clinics promising miracle cures are not a good idea at this time. The International Society for Stem Cell Research says: "Many clinics offering stem cell treatments make claims that are not supported by a current understanding of science."

Fortunately, there's a lot you can do to keep your stem cells healthy and your RealAge younger.

1) Protect your skin from excess sun exposure; use micronized zinc oxide 30 SPF sunscreen. Exposure to ultraviolet radiation from the sun and tanning beds and lamps is a leading cause of melanoma. New research shows that the trigger may be stem cells gone wild; melanoma may be related to the formation of carcinogenic stem cells.

2) Avoid hormone-disrupting chemicals such as BPA in plastics and phthalates in household goods and products. One study found that they disrupt development of stem cells needed for sperm production.

3) Don't overeat; eat whole foods, not chemicals. Steer clear of processed foods that dose you with preservatives, colorings, emulsifiers, added sugars and syrups. Continuous intake of sugary foods reduces stem cell vitality! A lab study found that reducing caloric intake by 20 percent can positively boost stem cell activity. We say, try it five days a month.

4) Get regular exercise. According to a new study out of the University of Rochester, loss of muscle stem cells is the driving force in loss of muscle tone and strength as you age. That makes it increasingly important to get two to three 30-minute sessions of strength-building exercises weekly. Aerobic effort (push it a bit) stimulates some stem cells to produce bone instead of fat.

5) Avoid excess radiation. Exposure to a dental X-ray, PET or CAT scan provides diagnostic benefits without immediate risks. But new evidence shows that accumulative exposure to radiation over a lifetime can have damaging effects on stem cells and organs. Opt for an MRI, not a CAT scan when possible; refuse dental X-rays unless necessary; follow guidelines for mammograms. And make sure your imaging center is accredited, personnel are credentialed, and they use weight-based and indication-based protocols.

Mehmet Oz, M.D. is host of "The Dr. Oz Show," and Mike Roizen, M.D. is Chief Wellness Officer and Chair of Wellness Institute at Cleveland Clinic.

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How to keep your stem cells young - The Garden City Telegram

The advanced technology offered by uBiome may enable us to detect harmful oral bacteria before they endanger the lives of these children - with just a bit saliva.

San Francisco, CA (PRWEB) August 08, 2017

uBiome, the leader in microbial genomics, has issued its latest Microbiome Impact Grant award to pediatric dentist and scientist Dr. Jeremy Horst of UCSF School of Medicine, who, along with colleagues in the UCSF Children's Oral Health Research Center, is carrying out research into the use of the oral microbiome as a non-invasive way of predicting and preventing blood infections in immunocompromised young bone marrow transplant patients.

Bone marrow transplants are used in order to replace damaged or diseased cells with non-cancerous stem cells that can, in turn, grow new, healthy cells. These transplants tend to be used when treatments for cancer have destroyed the bone marrows normal stem cells. Bone marrow, which is found at the core of bones, is where the body manufactures blood cells.

Bone marrow transplants can be either allogeneic or autologous. Allogeneic transplants occur when bone marrow is received from a donor. In autologous transplants, the patients own bone marrow is used, after being collected, frozen, and stored until it is needed following chemotherapy, for example.

Blood infections pose a considerable risk during bone marrow transplants, so being able to predict and prevent them is critical. Dr. Horsts study aims to explore the use of the oral microbiome as a predictive diagnostic for blood infections in pediatric patients who are immunocompromised, a common phenomenon during transplant procedures. Having a weakened immune system, technically known as immunodeficiency, is a state in which the immune systems ability to fight infectious disease and cancer is either compromised or entirely absent.

The potential to use the oral microbiome as a marker for the blood microbiome would offer considerable benefits, particularly because of its non-invasive nature.

Dr. Horst is a Postdoctoral Scholar in the Biochemistry and Biophysics Department at UCSF School of Medicine, specializing in Biochemistry and Infectious Diseases. He received his PhD for studies in Oral and Computational Biology at the University of Washington, after also first gaining his DDS there. This was followed by a residency in Pediatric Dentistry at UCSF. Dr. Horst began his academic studies at UCSD, where he was awarded his BS in Pharmacological Chemistry, a BA in Psychology, and a masters in Chemistry. He has contributed to 40 scientific papers.

The microbiome is the collective term for the ecosystem of trillions of microorganisms that live in and on the human body. Many play important parts in supporting life. For example, gut bacteria aid digestion and enable the synthesis of vitamins. Pathogenic bacteria, however, can be associated with a range of conditions. uBiome employs precision sequencing technology to generate detailed analyses of the human microbiome.

Dr. Jeremy Horst says: To prepare young patients for bone marrow transplant, their immune systems are temporarily wiped out. Despite our extraordinarily cautious efforts, one third of these children at UCSF Benioff Childrens Hospital get blood infections, and oddly enough, one third of the infections come from bacteria in the dental plaque. We use traditional culture-based diagnostics to understand these infections once they happen, but the advanced technology offered by uBiome may enable us to detect harmful oral bacteria before they endanger the lives of these children - with just a bit saliva.

Dr. Zachary Apte, co-founder and CTO of uBiome, adds: After collaborating with him in the past, were familiar with Dr. Horsts work. We think his novel proposal to predict and prevent blood infections in young patients with weakened immune systems using something as simple as a saliva test is very exciting.

Founded in 2012, uBiome is the worlds leading microbial genomics company. uBiome is funded by Y Combinator, Andreessen Horowitz, 8VC, and other leading investors.

uBiomes mission is to explore important research questions about the microbiome and to develop accurate and reliable clinical tests based on the microbiome.

Contact:Julie Taylorjulie(at)ubiome(dot)comPh: +1 (415) 212-9214

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uBiome Grant Will Enable UCSF Scientist to Explore 'Spit Test' to Predict Blood Infections in Young Bone Marrow ... - PR Web (press release)

In 2002, Ian Thompson, a specialist in facial reconstruction at Kings College, London, received an urgent phone call. A patient in his late 20s had been struck by an out-of-control car mounting the pavement. The impact had sent him catapulting over the bonnet of the car, smashing his face and shattering the fragile orbital floor the tiny bone, no more than 1mm thick, which holds the eyeball in place in the skull.

Without the orbital floor, your eye moves backwards into the skull, almost as a defensive mechanism, Thompson explains. But this results in blurred vision and lack of focus. This patient had also lost the ability to perceive colour. His job involved rewiring aircraft and as he could no longer detect a red wire from a blue one, hed barely been able to work in three years.

The accident had happened three years earlier. Since then, surgeons had desperately tried to reconstruct the bony floor and push the eye back into position, first using material implants and then bone from the patients own rib. Both attempts had failed. Each time, infection set in after a few months, causing extreme pain. And now the doctors were out of ideas.

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Thompsons answer was to build the worlds first glass implant, moulded as a plate which slotted in under the patients eye into the collapsed orbital floor. The idea of using glass a naturally brittle material to repair something so delicate may seem counterintuitive.

But this was no ordinary glass.

If you placed a piece of window glass in the human body, it would be sealed off by scar tissue, basically wobble around in the body for a while and then get pushed out, says Julian Jones, an expert in bioglass at Imperial College London. When you put bioglass in the body, it starts to dissolve and releases ions which kind of talk to the immune system and tell the cells what to do. This means the body doesnt recognise it as foreign, and so it bonds to bone and soft tissue, creating a good feel and stimulating the production of new bone.

Bioglass actually works even better than the patients own bone Ian Thompson

For Thompson, the results were immediate. Almost instantaneously, the patient regained full vision, colour and depth perception. Fifteen years on, he remains in full health.

Thompson has gone on to use bioglass plates to successfully treat more than 100 patients involved in car or motorcycle accidents. Bioglass actually works even better than the patients own bone, Thompson says. This is because weve found that it slowly leaches sodium ions as it dissolves, killing off bacteria in the local environment. So, quite by chance, you have this mild antibiotic effect which eliminates infections.

Cutting edge

Bioglass was invented by US scientist Larry Hench in 1969. Hench was inspired by a chance conversation on a bus with an army colonel who recently had returned from the Vietnam War. The colonel told Hench that while modern medical technology could save lives on the battlefield, it could not save limbs. Hench decided to shelve his research into intercontinental ballistic missiles and instead work on designing a bionic material which would not be rejected by the human body.

Hench ultimately took his research to London, and it has been in Britain where some of the most revolutionary bioglass innovations are being made in fields from orthopaedic surgery to dentistry.

Over the last 10 years, surgeons have used bioglass in a powdered form, which looks and feels like a gritty putty, to repair bone defects arising from small fractures. Since 2010, this same bioglass putty has hit the high street as the key component in Sensodynes Repair and Protect toothpaste, the biggest global use of any bioactive material. During the brushing process, the bioglass dissolves and releases calcium phosphate ions which bond to tooth mineral. Over time, they slowly stimulate regrowth.

But many scientists feel that the current applications of bioglass are barely scratching the surface of what could be possible. New clinical products are being developed which could revolutionise bone and joint surgery like never before.

Sitting in his office in Imperial Colleges Department of Materials, Jones is holding a small, cube-shaped object hes dubbed bouncy bioglass. Its similar to the current bioglass but with a slight twist: subtle alterations in the chemical composition mean its no longer brittle. Instead it bounces,like a kids power ball as Jones describes it, and its incredibly flexible.

The point of this is that it can be inserted into a badly broken leg and can support both the patients weight and allow them to walk on it without crutches, without requiring any additional metal pins or implants for support. At the same time, the bouncy bioglass also will stimulate and guide bone regrowth while slowly, naturally assimilating into the body.

To regenerate large pieces of bone, for example in a really big fracture, its very important to be able to put weight on your leg, Jones says. And its really important that the bio-implant in your leg is able to transmit the force from your weight to the bone cells, like a signal. Our body makes its own bone in the architecture that its in, because the cells feel the mechanical environment. So to grow back a big piece of bone you need to be able to transmit the right signals to them. The reason why astronauts in space lose bone mass is because without gravity, the cells arent receiving the same information as they do on Earth.

Further alterations to the chemical makeup of bioglass produce a different form which is much softer and has an almost rubbery feel. It feels almost like a piece of squid at a seafood restaurant. This bioglass is designed for possibly the holy grail of orthopaedic surgery: cartilage repair.

Right now, surgeons attempt to repair damaged cartilage in arthritic hips or damaged knee joints with a fiddly procedure called microfracture. This involves smoothing over the damaged area to expose the bone underneath, then pricking it to release stem cells from the bone marrow which stimulate repair. But this results in scar cartilage and within a few years, as many athletes have found, the original problem returns.

As a solution, Jones is looking to produce bioglass which can be 3D-printed and then slotted into any hole in the cartilage. For the cells to accept it, the material must retain all the natural properties of cartilage. To test its effectiveness, Jones uses a simulator that has human knee joints from cadavers donated for medical research.

We simulate the walking action, bending, all the things a knee would do, and make sure that the bioglass actually preserves the rest of the joint and behaves as it should do, he says. If that works then well proceed to animal and then clinical trials.

This same bioglass could find an additional use in aiding people with chronic back pain due to herniated discs. At the moment surgeons treat this by replacing the dysfunctional disc with a bone graft which fuses the vertebrae in the back together. But while this takes away the pain, it results in a considerable loss in mobility. Instead, a bioglass implant could be printed and simply inserted to replace the faulty disc.

It seems the obvious thing to do, Jones says. So far nobody has been able to replicate the mechanical properties of cartilage synthetically. But with bioglass, we think we can do it.

Weve just got to prove that we can. If all goes well and we pass all the necessary safety tests, it could reach the clinic in 10 years.

Using man-made materials which can fuse to the body may seem far-fetched but it is appearing to be a more and more likely component of future medicine. Already, millions of people brush their teeth with it. And that may just be the start.

This story is a part of BBC Britain a series focused on exploring this extraordinary island, one story at a time. Readers outside of the UK can see every BBC Britain story by heading to theBritain homepage; you also can see our latest stories by following us onFacebookandTwitter.

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The best way to fix broken bones might be with glass - BBC News

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How Newborn Foals' Dental Pulp Can Help Heal Horses TheHorse.com It is the most primitive form of stem cell tissue and has the greatest potential for developing into bone, ligaments, blood vessels, and more. Bertone and colleagues recently tested the effectiveness of dental pulp treatment in 20 lame horses with ...

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How Newborn Foals' Dental Pulp Can Help Heal Horses - TheHorse.com

EVANSTON - There hasnt been a gold standard for how orthopaedic spine surgeons promote new bone growth in patients, but now Northwestern University scientists have designed a bioactive nanomaterial that is so good at stimulating bone regeneration it could become the method surgeons prefer.

While studied in an animal model of spinal fusion, the method for promoting new bone growth could translate readily to humans, the researchers say, where an aging but active population in the U.S. is increasingly receiving this surgery to treat pain due to disc degeneration, trauma and other back problems. Many other procedures could benefit from the nanomaterial, ranging from repair of bone trauma to treatment of bone cancer to bone growth for dental implants.

The colored region in a micro-CT image shows regenerated high-quality bone in the spine with minimal use of growthfactor.Regenerative medicine can improve quality of life by offering less invasive and more successful approaches to promoting bone growth, said Samuel I. Stupp, who developed the new nanomaterial. Our method is very flexible and could be adapted for the regeneration of other tissues, including muscle, tendons and cartilage.

Stupp is director of Northwesterns Simpson Querrey Institute for BioNanotechnology and the Board of Trustees Professor of Materials Science and Engineering, Chemistry, Medicine and Biomedical Engineering.

For the interdisciplinary study, Stupp collaborated with Dr. Wellington K. Hsu, associate professor of orthopaedic surgery, and Erin L. K. Hsu, research assistant professor of orthopaedic surgery, both at Northwestern University Feinberg School of Medicine. The husband-and-wife team is working to improve clinically employed methods of bone regeneration.

Sugar molecules on the surface of the nanomaterial provide its regenerative power. The researchers studied in vivo the effect of the sugar-coated nanomaterial on the activity of a clinically used growth factor, called bone morphogenetic protein 2 (BMP-2). They found the amount of protein needed for a successful spinal fusion was reduced to an unprecedented level: 100 times less of BMP-2 was needed. This is very good news, because the growth factor is known to cause dangerous side effects when used in the amounts required to regenerate high-quality bone, and it is expensive as well.

The findings were published today (June 19) in the journal Nature Nanotechnology.

Stupps biodegradable nanomaterial functions as an artificial extracellular matrix, which mimics what cells in the body usually interact with in their surroundings. BMP-2 activates certain types of stem cells and signals them to become bone cells. The Northwestern matrix, which consists of tiny nanoscale filaments, binds the protein by molecular design in the way that natural sugars bind it in our bodies and then slowly releases it when needed, instead of in one early burst, which can contribute to side effects.

To create the nanostructures, the research team led by Stupp synthesized a specific type of sugar that closely resembles those used by nature to activate BMP-2 when cell signaling is necessary for bone growth. Rapidly moving flexible sugar molecules displayed on the surface of the nanostructures grab the protein in a specific spot that is precisely the same one used in biological systems when it is time to deploy the signal. This potentiates the bone-growing signals to a surprising level that surpasses even the naturally occurring sugar polymers in our bodies.

In nature, the sugar polymers are known as sulfated polysaccharides, which have super-complex structures impossible to synthesize at the present time with chemical techniques. Hundreds of proteins in biological systems are known to have specific domains to bind these sugar polymers in order to activate signals. Such proteins include those involved in the growth of blood vessels, cell recruitment and cell proliferation, all very important biologically in tissue regeneration. Therefore, the approach of the Stupp team could be extended to other regenerative targets.

Spinal fusion is a common surgical procedure that joins adjacent vertebra together using a bone graft and growth factors to promote new bone growth, which stabilizes the spine. The bone used in the graft can come from the patients pelvis an invasive procedure or from a bone bank.

There is a real need for a clinically efficacious, safe and cost-effective way to form bone, said Wellington Hsu, a spine surgeon. The success of this nanomaterial makes me excited that every spine surgeon may one day subscribe to this method for bone graft. Right now, if you poll an audience of spine surgeons, you will get 15 to 20 different answers on what they use for bone graft. We need to standardize choice and improve patient outcomes.

In the in vivo portion of the study, the nanomaterial was delivered to the spine using a collagen sponge. This is the way surgeons currently deliver BMP-2 clinically to promote bone growth.

The Northwestern research team plans to seek approval from the Food and Drug Administration to launch a clinical trial studying the nanomaterial for bone regeneration in humans.

We surgeons are looking for optimal carriers for growth factors and cells, Wellington Hsu said. With its numerous binding sites, the long filaments of this new nanomaterial is more successful than existing carriers in releasing the growth factor when the body is ready. Timing is critical for success in bone regeneration.

In the new nanomaterial, the sugars are displayed in a scaffold built from self-assembling molecules known as peptide amphiphiles, first developed by Stupp 15 years ago. These synthetic molecules have been essential in his work on regenerative medicine.

We focused on bone regeneration to demonstrate the power of the sugar nanostructure to provide a big signaling boost, Stupp said. With small design changes, the method could be used with other growth factors for the regeneration of all kinds of tissues. One day we may be able to fully do away with the use of growth factors made by recombinant biotechnology and instead empower the natural ones in our bodies.

The National Institute of Dental and Craniofacial Research of the National Institutes of Health (grant 5R01DE015920-10) and the Louis A. Simpson and Kimberly K. Querrey Center for Regenerative Nanomedicine at Northwestern University provided funding for this research.

The paper is titled Sulfated Glycopeptide Nanostructures for Multipotent Protein Activation. Stupp and Wellington and Erin Hsu are senior authors of the paper, and postdoctoral fellows Sungsoo Lee and Timmy Fyrner are first authors.

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Sugar-coated nanomaterial excels at promoting bone growth - Northwestern University NewsCenter

Officials announce the creation in Merida of a dental cryopreservation laboratory.

MERIDA With the increase in the exchange rate of the dollar, health tourism in Yucatan will generate even more than the three million dollars per year previously received. Mrida receives and treatsbetween three thousand and four thousand patients, said Armando Noguera Aguilar, general director of Dental Perfect, a company that will invest 25 million pesos in the city during 2017.

Armando Noguera Aguilar, general director of Dental Perfect (Photo: La Jornada Maya)

In a press conference at El Gran Caf, held in February, Noguer Aguilar said that dental health tourism treats seven million people each year in Mexico, so as Mrida turns into a cluster for the medical sector, there is an enormous potential to attract new customers.

The reason why there is health tourism in Merida, he explained, is because in the United States a dental implant can cost between five thousand and six thousand dollars, while in Yucatan only one thousand dollars.

To the state also come visitors from Europe, for the same economic benefit, he said. People prefer to go to Mexico, because they find the same quality with better prices, he said.

The investment of 25 million pesos to be held in Merida has as its objective the creation of three clinics and a laboratory for cryopreservation of dental stem cells, spaces that will create 150 direct jobs for skilled workers and 450 indirect ones; Its presence will increase dental health tourism by 25 percent, he predicted.

In about 10 years, dental stem cells will regenerate neuronal, bone, muscle, heart and some organs to treat problems such as Alzheimers or brain tumors.

With this scenario, he said that the quality of life of the human being is expected to increase in 10 years over the next decade, due to research in the branch worldwide, in places such as Germany, Switzerland and even Mexico.

Source: http://www.lajornadamaya.mx

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Health tourism's economic impact grows in Yucatan - The Yucatan Times

June 6, 2017 Drs. Carlos Isales, Meghan McGee-Lawrence, William D. Hill and Mark Hamrick. Credit: Phil Jones

With age, the form and function of our bones and muscles drop off, putting us as increased risk for frailty and falls.

Now researchers at the Medical College of Georgia at Augusta University are dissecting just what happens to the stem cells that make the tissues, which help keep us upright, with an eye on improving our healthspan.

Osteoporosis already is a major public health problem affecting about 44 million Americans and costing billions annually. The world's older population is growing at an unprecedented rate with 8.5 percent of the worldwide population - 617 million people - age 65 and older, a proportion estimated to reach 17 percent by 2050, according to the National Institute on Aging.

"After age 65 you start losing about 1 percent of both muscle and bone per year," said Dr. Carlos Isales, endocrinologist, Regents' professor and vice chair for clinical affairs in the MCG Department of Neuroscience and Regenerative Medicine.

"Daily exercise decreases the slope of that decline. But what we are focusing on is trying to see if we can flatten the curve even further," said Isales, principal investigator on a new $9.3 million Program Project grant from the National Institutes of Health.

Time seems to alter the dynamic between the mesenchymal stem cells making bone and muscle and the amino acids that fuel them. The MCG scientists also have evidence it changes the signals stem cells send each other.

The bottom line: Our stem cell population gets reduced and the cells we have become less efficient at making bone and muscle, often opting for the easier task of making fat instead, Isales said.

The team, which includes principal investigators bone biologist Dr. Mark Hamrick, stem cell researcher Dr. William D. Hill and biomedical engineer Dr. Meghan McGee-Lawrence, wants to keep stem cells focused on making bone and muscle.

"We are looking at stem cells as a group and what is happening to them as we age," Hill noted. "This includes a loss of direction so they aren't as functional as they were before. The other thing we are looking at is their survival and their numbers."

"We are trying to figure out why the changes are happening and if we can target those cells to make them want to make bone again," McGee-Lawrence said.

Much as the function of bone and muscle is interwoven, so is their health and the factors that promote their loss or survival also are similar, said Hamrick.

A major culprit in their breakdown appears to be the metabolite kynurenine, a byproduct of the essential amino acid tryptophan. Tryptophan is among the nine amino acids our body can't make and we must consume in foods like turkey and soybeans so we can perform essentials like making protein. The researchers also think the fuel sends signals to cells, ones that aging stem cells apparently don't get.

The unhealthy metabolite is the result of a natural action called oxidation, which occurs anytime cells use oxygen. Particularly with age, the free radicals produced by oxidation can also damage cells. Kynurenine results when the enzyme, indoleamine 2,3 dioxygenase, or IDO, which a variety of tissues make to help moderate an immune response, oxidizes tryptophan. Over time, kynurenine piles up and appears to alter the dynamic of bone and muscle formation.

Again, somewhat ironically, the many functions of essential amino acids include working as antioxidants, so the researchers are putting together nutrient cocktails - minus tryptophan and with reduced protein content - that they hope can reverse age-related damage. Isales notes that they may find that other amino acids produce similar problems as tryptophan in the aged environment.

So they also are taking more direct approaches like whether an IDO inhibitor - which is already in clinical trials as a cancer fighter - can reverse changes and get stem cells to regain more youthful function.

In an effort to begin to see if what they have seen in laboratory mice holds up in humans, they are trying both approaches in human stem cells retrieved during the process of a knee or hip replacement by colleagues in the MCG Department of Orthopaedic Surgery.

They have laboratory evidence that in mice at least, high kynurenine levels impact the ability of cells in the bone marrow to make bone-forming cells called osteoblasts. In fact, even relatively young mice fed kynurenine experience bone loss, an increase in bone destruction by cells called osteoclasts and increased fat in their bone marrow. Conversely, mice with IDO knocked out maintain strong bone mass.

"You can make an old mouse young and you can make a young mouse old," Hill noted.

The team also has evidence that part of how age-related increases in kynurenine does damage is by altering microRNAs - small but powerful pieces of RNA that can control expression of hundreds of genes at the same time - as well as vesicles called exosomes that are hauling the microRNAs around. Stem cells secrete exosomes as one way to communicate, and apparently aging stem cells don't communicate well with each other.

"Exosomes are one mechanism of crosstalk between cells and also between different organs," said Hamrick. "Your liver is producing exosomes, fat produces exosomes, they will hit other organs and they carry, in some cases, positive messages and in some cases bad messages," said Hamrick, who is leading this project to restore positive messaging.

They have laboratory evidence that aging alters at least two microRNAs, miR-141 and miR-183, which prompts cells to make bone-eating instead of bone-forming cells. Again, they have shown that even young stem cells exposed to older exosomes will assume this bone-reducing stance. But they also have some evidence that some of the dietary interventions Isales is looking at could reverse the ill effects.

The team recently reported in the journal Tissue Engineering that exosomes from old and younger mice were similar in size and number and both had a lot of miRNAs. But aged exosomes had significantly and specifically more mi183, an miRNA already associated with cancer. In this case, high mi183 appears to decrease cell proliferation and the ability of immature cells to become bone cells and to support the general deterioration that comes with age, called senescence. Age-related increases of reactive oxygen species and oxidative stress help increase mi183 levels and these undesirable results. When researchers treat mesenchymal stem cells from young animals with exosomes from old mice, is suppresses formation of muscle-making genes; giving mi183 directly to bone and muscle producing cells makes them start acting old. Now they want to know more about how aging changes the secretion and cargo of exosomes by mesynchymal stem cells and how that in turn contributes to bone and muscle loss.

A third project, led by Hill, will focus on the cargo, the miRNAs, to learn more about exactly how they impact bone formation and turnover. "We think that the amino acids are controlling the expression of specific sets of microRNA," Hill said. That means they may want to target and even eliminate key or critical microRNAs, which could obviously affect expression of numerous genes as a result.

They also are exploring aging's impact on stromal cell derived factor 1, or SDF-1, which is critical to helping keep stem cells in the bone marrow and focused on making bone. Age-related changes appear to make SDF-1 instead encourage stem cells to wander. The researchers note that while these cells do often need to leave the bone marrow, to say help heal an injury, these age-related travels are random and often cells don't find their way back. A consistent goal is identifying intervention targets.

"The idea is if we can change the environment and change how they are signaling to themselves and to other cells, we can modify the stem cell directly that way," Hill said.

They are looking upstream as well for earlier points of intervention, including what is happening to histone deacetylase-3, or HDAC3. They have evidence that HDAC3, another pervasive regulator in the body that can turn gene expression up or down, is important in stem cells' age-related propensity to make fat instead of bone.

At least one reason is that reduced HDAC3 means less bone, which literally makes more room for fat, said McGee-Lawrence, who is leading these studies. Her previous studies have shown that when HDAC3 is deleted from the skeleton, bones are weaker, much like what occurs with aging.

Now they have evidence that mice treated with kynurenine, for example, have suppressed HDAC3 expression in the bone. They want to know more about just how HDAC3 gets suppressed as we age and exactly what that does to bone formation and fat storage besides just making room. The new grant is allowing them to put the pieces together better, looking further at just what suppresses HDAC3 and what suppression does to bone versus fat formation. The bottom line again is identifying early points of intervention and potentially nutrients to intervene.

"Something in the microenvironment of the bone is causing the cells, instead of wanting to make bone, they are storing a lot of fat," McGee-Lawrence said. "Some of these epigenetic factors, like HDAC3, some of the environmental factors like changes in the amino acids are causing the cells to dysfunction. We are hoping to figure out what that signal is and how to reverse it and to make those cells want to start making bone again."

Identical twin studies have shown that environmental factors definitely play a role, since the bone/muscle health of these twins often is not identical even though their genes are, Isales said. Rather than changing the genes themselves, environmental factors appear to have changed their expression: which ones are turned or on off. These epigenetic changes include factors from diet to stress to sleep patterns to age.

There are 20 amino acids, which are essential to protein production and a variety of other functions from giving cells structure to helping organs functions. Kyrurenine also is associated with the degeneration of our brain and immune system as we age. Mesynchymal stem cells also produce blood, cartilage and fat cells.

Isales also is vice chair of clinical and translational research in the MCG Department of Orthopaedics and a faculty member in the MCG Department of Medicine. Hamrick, Hill and McGee-Lawrence are all faculty members in the MCG Department of Cellular Biology and Anatomy. Other scientists helping support three core laboratories for the interrelated studies include the Administrative Core with Biostatistics, Maribeth Johnson and Dr. Jie Chen, MCG Department of Biostatics and Epidemiology; the Bone Biology Core, Dr. Mohammed Elsalanty, Department of Oral Biology, Dental College of Georgia at AU; and the Bone Stem Cell Core, Dr. Xingming Shi, MCG Department of Neuroscience and Regenerative Medicine.

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Major research initiative explores how our bones and muscles age, new ways to block their decline - Medical Xpress

- More and more people retrieve their banked cells and benefit from clinical treatments

Twenty individuals, ranging from the ages of 2 to 43, have become the first to use stem cells from their teeth in the treatment of various conditions including cerebral palsy, diabetes, cleft lip, and autism. The cells in use are dental pulp stem cells (DPSCs) - the richest source of MSCs in the body - extracted from the likes of exfoliated incisors, deciduous or baby, and wisdom teeth.

All patients report no adverse reactions, with several experiencing huge improvements in their conditions. To date, all treatments worked as well if not better than traditional treatments, but by far the most promising results are being seen in children with autism.

A complex behavioural disorder that affects 1 in every 100 people in the UK, autism is one of the biggest challenges that faces modern medicine today. Not only do symptoms manifest differently in each patient, but there is no one definitive cause. To treat an individual requires a tailored combination of therapies and medications - often meaning years of harsh drugs and hours of intensive behavioural therapy.

Many experts believe stem cell therapy can change that, or at least help children along the way, and several recent studies are proving their intentions are more than good-hearted. Their case is based on the rationale that autism is caused, in part, by inflammation in the body. And a particular type of stem cells, known as mesenchymal stem cells (MSCs), is able to reduce that inflammation.

Our teeth are not only richer in MSCs than bone marrow or cord blood, but the process of extraction also costs less and can be done so non-invasively, using naturally fallen teeth. This makes it an easy and completely pain-free process. You don't even have to see the inside of a hospital or clinic - just send the tooth to the bank, and they will do the rest.

And that's exactly what the parents of five children with autism did. Having originally sent teeth of all shapes and sizes to BioEden, the world's first tooth stem cell bank, they've now retrieved their cells and the children are involved in various stages of cell-based therapies.

Reports from one 11-year-old show how developmental markers across the board improved after just 10 weeks of treatment. Progress has been made in language, driving motility, communication with the environment, and memory and retention, and they're getting ready for their second round of treatment this year.

In another case of an 11-year-old, the child didn't speak before the treatment but now has a vocabulary of 15 words. Other improvements among the five children include better memory, mobility, and bodily control, more energy, a new sensitivity to pain, and physical growth. It's clear autism responds well to tooth cells.

Tooth stem cell banking offers patients a convenient and risk-free alternative to cord blood banking for example and bone marrow aspiration. By not throwing away those shedded baby teeth and instead sending them to a specialist tooth bank, you can arm yourself with a powerful resource and help safeguard a children's future health.

BioEden is a specialist banking facility that does not directly participate in or encourage its customers to seek therapies. The determination as to whether stem cell therapy may be useful to treat a particular condition is a decision that must be made between the patient and their treating physician.

Contact: Leon Staff Tel.: +44-208-4770-336 Email: info@bioeden.co.uk

Website: http://www.bioeden.com

SOURCE BioEden

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BioEden - Autistic Children's Early Success Stories From Tooth Stem Cells - PR Newswire (press release)

(MENAFN Editorial) Stem cells are characterized by their potential to develop into fully functional cells of a specific organ or tissue in the body. Theoretically stem cells can be artificially coaxed into becoming a muscular cell, nerve cell or any other based on the medical requirement. This capability called Totipotency is sometimes lost along the development stages and cells then become pluripotent, multi-potent and oligopotent at each level. The stem cells of the body include embryonic stem cells, which are present in a blastocyst, fetal stem cells, cord blood stem cells (isolated from umbilical cord), adipose tissue, hematopoietic stem cells and dental stem cells. Stem cells and progenitor cells help act as a treatment and can perform as a damage repair mechanism of the body. Umbilical stem cells and embryonic stem cells can be stored in cryogenic-refrigeration as a stem cell storage bank for later use.

Stem cells have been applied in several therapies of late, particularly in oncology and brain disorders. The potential areas of stem cell therapy are limitless since the stem cells adapt to various body stimulus to convert into cells of unique function and type. This report covers the market for stem cell therapies, products and anti-bodies among other products in research pipelines of many key industrial players. The most common type of cells therapies commercialized today includes mesenchymal stem cells or MSCs. SCs used in osteo-grafting is one of the fastest growing market segments today. Research & development is carried out by government and private institutions on a very large scale since the success of even one application would mean the quickest means of treating severe and debilitating diseases and conditions. The most common proven treatments are targeted for bone, corneal and skin diseases. AMD in particular is a key target area within corneal treatments. BMT?s have been performed for over a decade successfully in most cases for autoimmune disorders, cancer and blood disorders among others. A rising application area is cosmetics wherein conditions such as alopecia are considered as strong growth factors.

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Ongoing research by SA-BRC estates suggest the market to be valued at US 6.5 billion in 2014 and growing at a CAGR of 16.8%. The major drivers of this therapy are the increase in the stem cell banking and cord blood banking market, which has increased the number of stem cell procedures. The stem cell banking market is thus complementing the stem cell therapy market. Another factor driving the growth is the list of potential applications. Several challenges are currently preventing the use of stem cells particularly in western countries, where intense regulatory hurdles have resulted in the slow progress in treatment approvals unlike countries such as China, where stem cell therapies have received a greater acceptance by the government and are practiced on a larger scope of therapies. Reimbursement and cost of treatment is expected to be one of the most significant challenges to this market since ethical issues as well cost incurred to hospital for technology used to complete all stages of stem cell therapies. Since several therapies are not covered for by insurance, out-of-pocket expenses are enormous in most experimental cases.

Stem cell therapy is relatively an old research area in biopharmaceutical and biotechnology. There are an estimated 2 million research projects covering all aspects of stem cell research over the world. There are over 400 clinical trials being conducted across the world for SC therapy products. Thus, there are numerous players involved in stem cell products of which the most notable key players are companies such as Cytori, Cardio3 Bioscience, Bioheart, Aastrom Biosciences, Invitrogen (part of Life Technologies), Osiris Therapeutics, TiGenix and Gamida Cell. The competitive landscape is highly fragmented and is expected to remain so due to high number of emerging players in the market leading to a high level of threat from new entrants.

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Proteomics applications in dental derived stem cells

Journal of Cellular Physiology, 2017, 232, 1602-1610 Jie Li, Weidong Tian and Jinlin Song

Abstract: At present, the existence of a variety of dental derived stem cells has been documented. These cells displayed promising clinical application potential not only for teeth and its surrounding tissue regeneration, but also for other tissues, such as nerve and bone regeneration. Proteomics is an unbiased, global informatics tool that provides information on all protein expression levels as well as post-translational modification in cells or tissues and is applicable to dental derived stem cells research. Over the last decade, considerable progress has been made to study the global proteome, secrotome, and membrane proteome of dental derived stem cells. Here, we present an overview of the proteomics studies in the context of stem cell research. Particular attention is given to dental derived stem cell types as well as current challenges and opportunities.

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June 2, 2017 by Mirabai Vogt-James A bone densitometer will accompany the mice to the space station. It measures the bone density of the animals. Credit: University of California, Los Angeles

What do space travel, rodents and a bone-building protein all have in common? A team of UCLA scientists is bringing these three elements together to test an experimental drug that could one day result in a treatment for osteoporosis, which affects more than 200 million people worldwide.

The drug could also potentially help those with bone damage or loss, a condition that afflicts people with traumatic bone injury, such as injured military service members, as well as astronauts who lose bone density while in space.

Led by Dr. Chia Soo and Dr. Kang Ting, who met and married while working on this project, as well as Dr. Ben Wu, the UCLA research team is scheduled to send 40 rodents to the International Space Station this week. Once there, the rodents will receive injections of the experimental drug, which is based on a bone-building protein called NELL-1. The project is being done in collaboration with NASA and the Center for the Advancement of Science in Space, which manages the U.S. National Laboratory on the space station.

"This is really a pivotal point in the study of NELL-1's effect on bone density," said Soo, principal investigator on the study, the vice chair for research in the UCLA Division of Plastic and Reconstructive Surgery, and a member of the UCLA Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research. "We would not be at this point without many years of funding and support from the National Institutes of Health, the California Institute for Regenerative Medicine and several UCLA departments and centers. We are honored to conduct the next phase of our research in the U.S. National Laboratory."

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The UCLA researchers have been conducting studies on NELL-1 for more than 18 years and were excited when Julie Robinson, NASA's chief scientist for the International Space Station Program, visited UCLA in early 2014 and encouraged them to submit a grant that would fund their NELL-1 research in space. The team received the necessary funding from the Center for the Advancement of Science in Space in September 2014 to move forward with the project.

"The preparations have been very exciting; we've had conference calls with NASA's Ames Research Center every two weeks to go over all the fine details," said Dr. Jin Hee Kwak, an assistant professor of orthodontics in the UCLA School of Dentistry and project manager on the study. "Everything is choreographed down to the tiniest details, such as whether you're going to fill a syringe half way or all the waythat small amount affects the total weight of the rocket."

SpaceX's Dragon spacecraft is currently targeted to blast off from Kennedy Space Center in Florida today. It will be the first time that UCLA scientists send rodents to the International Space Station. After living in microgravity and receiving NELL-1 injections for about four weeks, half of the rodents will return from space and land in the Pacific Ocean off the coast of Baja, California.

This marks the first time that American researchers will bring back live rodents from the International Space Station. After retrieval, the rodents will be returned to UCLA where they will continue to receive the NELL-1 drug for an additional four weeks. The remaining half of the rodents that stay in the space station will also receive an additional four-week dosage of the drug and will return to UCLA later.

"To prepare for the space project and eventual clinical use, we chemically modified NELL-1 to stay active longer," said Wu, who is chair of the division of advanced prosthodontics in the UCLA School of Dentistry and professor in the schools of engineering and medicine. "We also engineered the NELL-1 protein with a special molecule that binds to bone, so the molecule directs NELL-1 to its correct target, similar to how a homing device directs a missile."

Discovered in 1996 by Ting, NELL-1 has a powerful effect on tissue-specific stem cells that create bone-building cells called osteoblasts. When exposed to NELL-1, the stem cells create osteoblasts that are much more effective at building bone. Furthermore, NELL-1 reduces the function of osteoclasts, which are the cells that break down bone.

"Our preclinical studies show that NELL-1's dual effect on both osteoblasts and osteoclasts significantly increases bone density," said Ting, chair of the section of orthodontics and the division of growth and development in the UCLA School of Dentistry.

After the age of 50, humans typically lose about 0.5 percent of their bone mass each year. But in space, bone loss significantly increases due to the lack of gravity. It is commonly known that bone density is improved by physical activity that puts pressure on bone, which helps it stay strong. Without gravity's pressure, astronauts can lose around 1.5 percent of their bone mass each month. Therefore, space is an ideal testing environment for NELL-1's effect on bone density.

Research on NELL-1 is supported by past or current grants from the National Institute of Dental and Craniofacial Research, the National Institute of Arthritis and Musculoskeletal and Skin Diseases, the California Institute for Regenerative Medicine, the UCLA Broad Stem Cell Research Center, the UCLA School of Dentistry, the UCLA Department of Orthopaedic Surgery and the UCLA Orthopaedic Hospital Research Center.

The experimental NELL-1 drug described above is used in preclinical tests only and has not been tested in humans or approved by the Food and Drug Administration as safe and effective for use in humans.

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Mice headed for space to test bone-building drug - Medical Xpress