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The association of ALT to HDL-C ratio with type 2 diabetes in 5074 years old adults: a population-based study ... - Nature.com
Eyeglasses Improve Income as Well as Sight, Study Shows The New York Times
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Eyeglasses Improve Income as Well as Sight, Study Shows - The New York Times
Biotherapeutics
January 29, 2022
2021 has been a year of significant innovation across the field of regenerative medicine at Mayo Clinic. Important advancements in preclinical research, as well as new regenerative treatments for patients, further are solidifying Mayo Clinics reputation as a world-class leader in regenerative medicine.
Regenerative medicine is still a relatively new field of practice, representing a paradigm shift from the traditional focus of health care of fighting disease to rebuilding health. Mayo Clinic's Center for Regenerative Medicine is leveraging its unique expertise, resources and capabilities to create the worlds most advanced and innovative ecosystem for the development, manufacture and delivery of novel regenerative biotherapeutics.
New directions in biomanufacturing
Mayo Clinic is focused on a newly refreshed strategy in regenerative medicine this year one that emphasizes an enhanced capability for biomanufacturing, with technology platforms supporting the development of new therapeutics known as biologics. Biologics are a new type of "drug" derived from living organisms that have the potential for targeted healing with fewer side effects. Many of these next-generation therapeutics can be scaled and mass produced for patients at Mayo Clinic and around the world. The Center for Regenerative Medicine is leading Mayos enterprise biomanufacturing strategy in close collaboration with Research, Practice and Education leaders and key stakeholders, including theCancer Center,Center for Individualized Medicine,Department of Laboratory Medicine and Pathology,Mayo Clinic Ventures, Mayo ClinicPlatform,Center for Digital Healthand Mayo ClinicInternational.
In August, Mayo welcomed Julie Allickson, Ph.D., as the Michael S. and Mary Sue Shannon Family Director of Mayo Clinic's Center for Regenerative Medicine and the Otto Bremer Trust director of Biomanufacturing and Product Development in the Center for Regenerative Medicine, and she will lead the execution of Mayos biomanufacturing strategy. Dr. Allickson joined Mayo Clinic from the Institute for Regenerative Medicine at Wake Forest School of Medicine in North Carolina.
"This is an exciting time in regenerative medicine, a new era with great promise for the impact that these new therapies and procedures can have for patients," says Dr. Allickson. "I am looking forward to working collaboratively with colleagues across the enterprise to position Mayo Clinic as the global leader in scientific discovery and clinical practice advancement in regenerative medicine."
Significant investments in biomanufacturing facilities continued this year with the buildout of current Good Manufacturing Practices facilities on all three Mayo campuses.These facilities meet strict quality controls and regulatory guidelines that are required for manufacturing new biologics. The long-term goal is to have these new types of healing solutions on-site where they can be used immediately for patients with unmet needs. Mayo will focus on biomanufacturing across seven prioritized technology platforms:
Research that advances the practice
From helping establish common terminology for regenerative medicine to discovering new ways of manufacturing cardiopoietic stem cells with heart healing potential for select patients with advanced heart failure, Mayo Clinic physicians and scientists have made significant advancements in the discovery-translation-application continuum in regenerative medicine. Examples include:
Difficult-to-treat, chronic wounds healed with normal scar-free skin in preclinical models after treatment with an acellular product discovered at Mayo Clinic. Derived from platelets, the purified exosomal product, known as PEP, was used to deliver healing messages into cells of animal models of ischemic wounds. In a groundbreaking study published in Theranostics, the Mayo Clinic research team documented restoration of skin integrity, hair follicles, sweat glands, skin oils and normal hydration.
A Mayo Clinic collaborative study documented a remote-controlled bronchoscope functioned like a GPS system, tracking hard-to-find lung masses and accurately biopsying them. This multisite research, published in Annals of Thoracic Surgery, lays the foundation for precisely finding early stage cancer when it is most treatable, and targeting it with regenerative biotherapeutics needed to stimulate healing.
"In the past, we didn't have a reliable way of reaching these nodules in the lungs from within the airway. This is a very small catheter that gets almost anywhere, and is able to access and biopsy lung nodules," says Janani Reisenauer, M.D., first author on the study and a Mayo Clinic thoracic surgeon. "It's very similar to driving a car and having your normal street view with the aid of the GPS in your car telling you in real-time where to turn right and left to arrive at your destination."
Mayo Clinic researchers biomanufactured chimeric antigen receptor-T cell therapy (CAR-T cell therapy) in a new way to track the cells' cancer fighting journey and predict toxic side effects. This Mayo Clinic breakthrough, published in Cancer Immunology Research, could make this immunotherapy easier for patients to tolerate. Perhaps more importantly, it could unravel the mystery of how to expand CAR-T cell therapy to more types of cancers.
"This new technology allows us to image CAR-T cells after they are given to patients and study their fate," says Saad Kenderian, M.B., Ch.B., a Mayo Clinic hematologist and researcher, and lead author. "This allows us to investigate strategies that could improve CAR-T cell trafficking and penetration into the tumor cells, and thus canimprove tumor killing."
Mayo Clinic is applying regenerative medicine to cosmetic services aimed at resetting the body's clock to a time of more youthful function and appearance. Regenerative procedures, such as platelet-rich plasma to rejuvenate aging skin and stimulate hair growth for people with alopecia or baldness, are offered on all three campuses. Many regenerative services go beyond cosmetics to facial reconstruction after disease, cancer or traumatic injury. For example, The Multidisciplinary Cosmetic Center at Mayo Clinic in Arizona pairs general and facial plastic surgery with dermatologists, gynecologists, vascular surgeons, urologists and aestheticists to deliver services grounded in scientific evidence and the latest regenerative technologies.
Training the emerging regenerative sciences workforce
A well-trained regenerative science workforce is needed to apply the newest discoveries to clinical care. Mayo Clinic has made significant strides this past year in educating future physicians, scientists and allied health staff in regenerative medicine.
Mayo Clinic achieved an important milestone when it admitted its first five students as inaugural scholars in the newly established Regenerative Sciences Track within the Ph.D. program in the Mayo Clinic Graduate School of Biomedical Sciences. The new doctoral program that began this fall fulfills Mayo's objective of providing first-of-its-kind education in the evolving field of regenerative science and medicine
Taught by regenerative science and medicine experts, the curriculum embraces a training paradigm that includes fundamental cellular and molecular science principles, and transdisciplinary education in regulatory issues, quality control, bio-business and entrepreneurial pathways, data science, medical sciences, ethics, and emerging technologies.
Throughout the four-day symposium, experts at Mayo Clinic and around the world shared regenerative medicine applications to aging, musculoskeletal conditions, lung diseases, organ transplantation and cancer. The symposium featured presentations on promising research, navigating regulatory pathways and seeking opportunities for commercialization.
Peter Marks, M.D., Ph.D.,director of the Food and Drug Administration (FDA) Center for Biologics Evaluation made a virtual presentation where he pledged FDA support for regenerative technologies that offer new solutions for unmet patient needs.
Another promising year in 2022
Mayo Clinic in Arizona is among the first to offer larynx transplantation and is currently evaluating patients for this landmark surgery. In addition, Center for Regenerative Medicine continues to support initiatives, such as expanding of CAR-T therapy and making organ transplantation more available and successful for patients.
New advanced biomanufacturing facilities will be operational in One Discovery Square in Rochester and in the Discovery & Innovation Building in Florida. Biomanufacturing expansion on the Phoenix campus will be strategically assessed as the buildout of Arizona "Bold. Forward" continues. The Center for Regenerative Medicine continues to spur innovation to rapidly advance novel regenerative therapies into the clinic to support Mayo Clinic's 2030 Vision to cure, connect and transform care.
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Science Saturday: A year of new directions and advancements for ...
Mating Study Unlocks the Genetic Code of Attraction Neuroscience News
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Mating Study Unlocks the Genetic Code of Attraction - Neuroscience News
Editors Note: This is the second article in a two-part series exploring the promise and limitations of the field of personalized medicine. The first part focused on advances and innovation in the field.
In the mid-1990s, researchers identified two gene mutations that are key to predicting genetic susceptibility to breast cancer: BRCA1 and BRCA2. In 1996, the BRCA1/2 mutation screening became the first genetic test for cancer risk available as a clinical service.
This genetic screening was an early innovation in a field that has come to be known as personalized medicine, which can be applied across a variety of medical specialties. Its defining characteristic is that a patients health care team takes into consideration a wide range of factors such as genetics, lifestyle, diet, specifics of disease presentation, and living environment when deciding on an individualized prevention or treatment plan.
With the advent of personalized medicine, including genetic screening as well as more targeted cancer drugs and therapies, the death rate for breast cancer in the United States declined by 43% from 1989 to 2020, according to the American Cancer Society (ACS). But even as mortality from breast cancer has decreased overall, there are statistics that highlight inequities in outcomes. Despite Black women having a lower incidence of breast cancer than non-Hispanic White women, Black women of all ages die from breast cancer at a 40% higher rate than non-Hispanic White women, and Black women under 50 years old die of breast cancer at twice the rate of non-Hispanic White women in the same age category.
Research shows that Black women get the BRCA1/2 screening less often than White women, at least in part because it is offered to them less frequently. One 2017 study found that, of women under 50 years old diagnosed with invasive breast cancer in Florida, 85.7% of the White women in the study were referred for genetic testing, while only 37% of the Black women were.
This is just one example of the inequities that some medical researchers and health equity advocates say severely limit the benefits of personalized medicine, even as technology advances.
[Personalized medicine] products are informative and are having an impact in certain communities, but its not equitable across all communities, says Rick Kittles, PhD, senior vice president for research at Morehouse School of Medicine, a historically Black medical college (HBCU) in Atlanta.
In the United States, people who are Black, Hispanic or Latino, American Indian or Alaska Native, people with low incomes, people who are uninsured or underinsured, and those who live in rural areas, as well as others who have been marginalized, face multiple barriers to personalized medicine. These barriers include a lack of inclusion of diverse genetics in research, the high cost of genetic testing and technology used in personalized medicine, and a lack of awareness of and education about personalized medicine among health care providers outside of urban medical centers. Some sociologists hypothesize that advances in medical innovation may, in fact, exacerbate existing inequities because people with economic and educational advantage are more likely to access care that improves lives and reduces mortality, while those from marginalized communities are left behind.
Its a problem that several academic medical centers are seeking to address with a range of strategies, from expanding personalized medicine research at HBCU medical schools to engaging community partners for research recruitment.
The field of human genetics has grown exponentially since the 2003 completion of the Human Genome Project, an international research effort that mapped the gene pairs that make up human DNA. The endeavor found that all humans share 99.9% of the same genome, with the other 0.1% accounting for all genetic diversity among individuals. Within that 0.1% are the wide variety of heritable traits, from physical characteristics to genetic mutations that cause or increase risk for certain diseases.
And yet, in the more than 6,000 genome-wide association studies (when researchers scan the genomes of large populations to try to identify genetic variations associated with diseases) that have been published internationally over the last two decades, 90% of all people analyzed were of European descent, according to a 2023 article in the Human Molecular Genetics journal.
This means that researchers have very little understanding of heritable disease risk for the vast majority of the worlds population when it differs from the variations seen in people of European descent.
Kittles, who is a genetic epidemiologist by trade, joined Morehouse in 2022 to lead the medical schools expanding efforts to advance medical research focusing on the inclusion of people from groups that have historically been excluded from clinical research and underserved in health care.
Among his faculty recruits is Melissa B. Davis, PhD, a genetics researcher focused on racial disparities in cancer who will lead the schools new Institute of Genomic Medicine. Davis previous work includes identifying two genes found in women of African ancestry that may increase their likelihood of developing an aggressive form of breast cancer, much like the BRCA1/2 gene.
For women of color who get tested [for BRCA 1/2], the benefit of that test is not equitable and in many cases the tests come back unknown, Kittles says. Thats because those variants [that are found in people of African descent] are not in databases Its a glaring, prime example of where we are in precision medicine right now.
The research expansion at Morehouse is funded by an $11.5 million grant from the Chan Zuckerberg Initiative (CZI, created by Facebook founder Mark Zuckerberg and his wife, Priscilla Chan) and is part of the charitable foundations larger Accelerate Precision Health program. CZI has granted equal funds to each of the nations three other HBCU medical schools: Charles Drew University College of Medicine in Los Angeles; Howard University College of Medicine in Washington, D.C.; and Meharry Medical College in Nashville.
When we think about the science we want to support, [we ask,] Who does the science? What science is being done? Who does the science serve? says Bil Clemons, PhD, science program officer for Diversity, Equity, and Inclusion in Science for CZI. Fundamentally, Is the science that were doing inclusive of everyone?
Most of the funding from CZI has gone to hiring faculty at HBCU medical schools to bolster their capacity to expand their research footprint over time, but its also funded the creation of new programs to train genetic counselors at Charles Drew University College of Medicine.
Kittles says that CZIs funding is instrumental to advancing research into genetic diversity and health disparities at HBCU medical schools, particularly because these institutions have often been overlooked for federal and philanthropic funding in the past.
That creates a disparity that not only limits the research impact of those institutions, but also the health of the communities that they serve, says Kittles. So much so that while all HBCUs have strong teaching experience, the development of research has been hampered because of the lack of funding and the ability to bring in talent who want to do research. The sustainability of research is limited because of that history.
In turn, thats set back progress in reducing health disparities, especially in Black communities and other communities of color, Kittles says, because HBCU medical schools tend to have more trust and access to those communities than many other medical centers.
Many academic medical centers historically have had a very strong disconnect with disparate communities, Kittles explains. The bulk of their research and the bulk of their patients are not diverse And so, when they do research, theyre limited in terms of their touch.
In addition to the efforts at the HBCU medical schools, dozens of medical centers are participating in the National Institutes of Health (NIH) All of Us research program, the goal of which is to build one of the largest and most diverse health databases in the world.
The All of Us program is studying patients social determinants of health, a phrase that refers to the various factors such as environment, socioeconomic status, access to healthy food, and access to health care that can affect health.
The NIH has funded and partnered with more than a dozen organizations to expand their reach into the communities that are historically underrepresented in biomedical research, including the American Association on Health and Disability; the National Alliance for Hispanic Health; and the National Baptist Convention, USA Inc.; among others. These organizations use their connections within marginalized communities to enroll and retain participants in the program. As of September 2021, the partners had helped enroll more than 400,000 participants, 80% of whom are from communities that are historically underrepresented in research. The study aims to provide a holistic picture of health by collecting samples of blood, urine, and saliva; physical measurements; electronic health records; health and family medical histories; information about lifestyles and communities; and data from wearable technologies, such as smartwatches, according to the NIH.
And while this and other endeavors are a step forward, Kittles says that all academic medical centers have a responsibility to resolve inequities in their own communities in order to truly make progress in advancing accessibility to personalized medicine.
In my career, Ive been at resource-rich [institutions], and resource-poor [institutions], and what I call community-rich and community-poor. Some had strong relationships with the community, and others had no trust from communities around them, says Kittles. When we talk about health equity, there has to be a commitment that goes beyond the window dressings and the social media tags that you see Part of that is bringing individuals into the institution that represent the communities that you want to benefit.
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Personalized medicine is coming, but who will have access to it?
MU Researchers Participating in International Clinical Study Targeting Prevention of Osteoarthritis University of Missouri School of Medicine
Stem Cell Investig. 2019; 6: 19.
1Stem Cell Research Center, Tabriz University of Medical Sciences, Tabriz, Iran;
2Department of Clinical Sciences, Faculty of Veterinary Medicine, University of Tabriz, Tabriz, Iran;
2Department of Clinical Sciences, Faculty of Veterinary Medicine, University of Tabriz, Tabriz, Iran;
3Hematology and Oncology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
1Stem Cell Research Center, Tabriz University of Medical Sciences, Tabriz, Iran;
2Department of Clinical Sciences, Faculty of Veterinary Medicine, University of Tabriz, Tabriz, Iran;
3Hematology and Oncology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
Contributions: (I) Conception and design: E Fathi, R Farahzadi; (II) Administrative support: E Fathi, R Farahzadi; (III) Provision of study materials or patients: None; (IV) Collection and assembly of data: R Farahzadi, N Rajabzadeh; (V) Data analysis and interpretation: All authors; (VI) Manuscript writing: All authors; (VII) Final approval of manuscript: All authors.
#These authors contributed equally to this work.
Received 2018 Nov 11; Accepted 2019 Mar 17.
Recent developments in the stem cell biology provided new hopes in treatment of diseases and disorders that yet cannot be treated. Stem cells have the potential to differentiate into various cell types in the body during age. These provide new cells for the body as it grows, and replace specialized cells that are damaged. Since mesenchymal stem cells (MSCs) can be easily harvested from the adipose tissue and can also be cultured and expanded in vitro they have become a good target for tissue regeneration. These cells have been widespread used for cell transplantation in animals and also for clinical trials in humans. The purpose of this review is to provide a summary of our current knowledge regarding the important and types of isolated stem cells from different sources of animal models such as horse, pig, goat, dog, rabbit, cat, rat, mice etc. In this regard, due to the widespread use and lot of attention of MSCs, in this review, we will elaborate on use of MSCs in veterinary medicine as well as in regenerative medicine. Based on the studies in this field, MSCs found wide application in treatment of diseases, such as heart failure, wound healing, tooth regeneration etc.
Keywords: Mesenchymal stem cells (MSCs), animal model, cell-based therapy, regenerative medicine
Stem cells are one of the main cells of the human body that have ability to grow more than 200 types of body cells (1). Stem cells, as non-specialized cells, can be transformed into highly specialized cells in the body (2). In the other words, Stem cells are undifferentiated cells with self-renewal potential, differentiation into several types of cells and excessive proliferation (3). In the past, it was believed that stem cells can only differentiate into mature cells of the same organ. Today, there are many evidences to show that stem cells can differentiate into the other types of cell as well as ectoderm, mesoderm and endoderm. The numbers of stem cells are different in the tissues such as bone marrow, liver, heart, kidney, and etc. (3,4). Over the past 20 years, much attention has been paid to stem cell biology. Therefore, there was a profound increase in the understanding of its characteristics and the therapeutic potential for its application (5). Today, the utilization of these cells in experimental research and cell therapy represents in such disorders including hematological, skin regeneration and heart disease in both human and veterinary medicine (6).The history of stem cells dates back to the 1960s, when Friedenstein and colleagues isolated, cultured and differentiated to osteogenic cell lineage of bone marrow-derived cells from guinea pigs (7). This project created a new perspective on stem cell research. In the following, other researchers discovered that the bone marrow contains fibroblast-like cells with congenic potential in vitro, which were capable of forming colonies (CFU-F) (8). For over 60 years, transplantation of hematopoietic stem cells (HSCs) has been the major curative therapy for several genetic and hematological disorders (9). Almost in 1963, Till and McCulloch described a single progenitor cell type in the bone marrow which expand clonally and give rise to all lineages of hematopoietic cells. This research represented the first characterization of the HSCs (10). Also, the identification of mouse embryonic stem cells (ESCs) in 1981 revolutionized the study of developmental biology, and mice are now used extensively as one of the best option to study stem cell biology in mammals (11). Nevertheless, their application a model, have limitations in the regenerative medicine. But this model, relatively inexpensive and can be easily manipulated genetically (12). Failure to obtain a satisfactory result in the selection of many mouse models, to recapitulate particular human disease phenotypes, has forced researchers to investigate other animal species to be more probably predictive of humans (13). For this purpose, to study the genetic diseases, the pig has been currently determined as one the best option of a large animal model (14).
Stem cells, based on their differentiation ability, are classified into different cell types, including totipotent, pluripotent, multipotent, or unipotent. Also, another classification of these cells are based on the evolutionary stages, including embryonic, fetal, infant or umbilical cord blood and adult stem cells (15). shows an overview of stem cells classifications based on differentiation potency.
An overview of the stem cell classification. Totipotency: after fertilization, embryonic stem cells (ESCs) maintain the ability to form all three germ layers as well as extra-embryonic tissues or placental cells and are termed as totipotent. Pluripotency: these more specialized cells of the blastocyst stage maintain the ability to self-renew and differentiate into the three germ layers and down many lineages but do not form extra-embryonic tissues or placental cells. Multipotency: adult or somatic stem cells are undifferentiated cells found in postnatal tissues. These specialized cells are considered to be multipotent; with very limited ability to self-renew and are committed to lineage species.
Toti-potent cells have the potential for development to any type of cell found in the organism. In the other hand, the capacity of these cells to develop into the three primary germ cell layers of the embryo and into extra-embryonic tissues such as the placenta is remarkable (15).
The pluripotent stem cells are kind of stem cells with the potential for development to approximately all cell types. These cells contain ESCs and cells that are isolated from the mesoderm, endoderm and ectoderm germ layers that are organized in the beginning period of ESC differentiation (15).
The multipotent stem cells have less proliferative potential than the previous two groups and have ability to produce a variety of cells which limited to a germinal layer [such as mesenchymal stem cells (MSCs)] or just a specific cell line (such as HSCs). Adult stem cells are also often in this group. In the word, these cells have the ability to differentiate into a closely related family of cells (15).
Despite the increasing interest in totipotent and pluripotent stem cells, unipotent stem cells have not received the most attention in research. A unipotent stem cell is a cell that can create cells with only one lineage differentiation. Muscle stem cells are one of the example of this type of cell (15). The word uni is derivative from the Latin word unus meaning one. In adult tissues in comparison with other types of stem cells, these cells have the lowest differentiation potential. The unipotent stem cells could create one cell type, in the other word, these cells do not have the self-renewal property. Furthermore, despite their limited differentiation potential, these cells are still candidates for treatment of various diseases (16).
ESCs are self-renewing cells that derived from the inner cell mass of a blastocyst and give rise to all cells during human development. It is mentioned that these cells, including human embryonic cells, could be used as suitable, promising source for cell transplantation and regenerative medicine because of their unique ability to give rise to all somatic cell lineages (17). In the other words, ESCs, pluripotent cells that can differentiate to form the specialized of the various cell types of the body (18). Also, ESCs capture the imagination because they are immortal and have an almost unlimited developmental potential. Due to the ethical limitation on embryo sampling and culture, these cells are used less in research (19).
HSCs are multipotent cells that give rise to blood cells through the process of hematopoiesis (20). These cells reside in the bone marrow and replenish all adult hematopoietic lineages throughout the lifetime of the human and animal (21). Also, these cells can replenish missing or damaged components of the hematopoietic and immunologic system and can withstand freezing for many years (22).The mammalian hematopoietic system containing more than ten different mature cell types that HSCs are one of the most important members of this. The ability to self-renew and multi-potency is another specific feature of these cells (23).
Adult stem cells, as undifferentiated cells, are found in numerous tissues of the body after embryonic development. These cells multiple by cell division to regenerate damaged tissues (24). Recent studies have been shown that adult stem cells may have the ability to differentiate into cell types from various germ layers. For example, bone marrow stem cells which is derived from mesoderm, can differentiate into cell lineage derived mesoderm and endoderm such as into lung, liver, GI tract, skin, etc. (25). Another example of adult stem cells is neural stem cells (NSCs), which is derived from ectoderm and can be differentiate into another lineage such as mesoderm and endoderm (26). Therapeutic potential of adult stem cells in cell therapy and regenerative medicine has been proven (27).
For the first time in the late 1990s, CSCs were identified by John Dick in acute myeloid diseases. CSCs are cancerous cells that found within tumors or hematological cancers. Also, these cells have the characteristics of normal stem cells and can also give rise to all cell types found in a particular cancer sample (28). There is an increasing evidence supporting the CSCs hypothesis. Normal stem cells in an adult living creature are responsible for the repair and regeneration of damaged as well as aged tissues (29). Many investigations have reported that the capability of a tumor to propagate and proliferate relies on a small cellular subpopulation characterized by stem-like properties, named CSCs (30).
Embryonic connective tissue contains so-called mesenchymes, from which with very close interactions of endoderm and ectoderm all other connective and hematopoietic tissues originate, Whereas, MSCs do not differentiate into hematopoietic cell (31). In 1924, Alexander A. Maxi mow used comprehensive histological detection to identify a singular type of precursor cell within mesenchyme that develops into various types of blood cells (32). In general, MSCs are type of cells with potential of multi-lineage differentiation and self-renewal, which exist in many different kinds of tissues and organs such as adipose tissue, bone marrow, skin, peripheral blood, fallopian tube, cord blood, liver and lung et al. (4,5). Today, stem cells are used for different applications. In addition to using these cells in human therapy such as cell transplantation, cell engraftment etc. The use of stem cells in veterinary medicine has also been considered. The purpose of this review is to provide a summary of our current knowledge regarding the important and types of isolated stem cells from different sources of animal models such as horse, pig, goat, dog, rabbit, cat, rat, mice etc. In this regard, due to the widespread use and lot of attention of MSCs, in this review, we will elaborate on use of MSCs in veterinary medicine.
The isolation method, maintenance and culture condition of MSCs differs from the different tissues, these methods as well as characterization of MSCs described as (36). MSCs could be isolated from the various tissues such as adipose tissue, bone marrow, umbilical cord, amniotic fluid etc. (37).
Diagram for adipose tissue-derived mesenchymal stem cell isolation (3).
Diagram for bone marrow-derived MSCs isolation (33). MSC, mesenchymal stem cell.
Diagram for umbilical cord-derived MSCs isolation (34). MSC, mesenchymal stem cell.
Diagram for isolation of amniotic fluid stem cells (AFSCs) (35).
Diagram for MSCs characterization (35). MSC, mesenchymal stem cell.
The diversity of stem cell or MSCs sources and a wide aspect of potential applications of these cells cause to challenge for selecting an appropriate cell type for cell therapy (38). Various diseases in animals have been treated by cell-based therapy. However, there are immunity concerns regarding cell therapy using stem cells. Improving animal models and selecting suitable methods for engraftment and transplantation could help address these subjects, facilitating eventual use of stem cells in the clinic. Therefore, for this purpose, in this section of this review, we provide an overview of the current as well as previous studies for future development of animal models to facilitate the utilization of stem cells in regenerative medicine (14). Significant progress has been made in stem cells-based regenerative medicine, which enables researchers to treat those diseases which cannot be cured by conventional medicines. The unlimited self-renewal and multi-lineage differentiation potential to other types of cells causes stem cells to be frontier in regenerative medicine (24). More researches in regenerative medicine have been focused on human cells including embryonic as well as adult stem cells or maybe somatic cells. Today there are versions of embryo-derived stem cells that have been reprogrammed from adult cells under the title of pluripotent cells (39). Stem cell therapy has been developed in the last decade. Nevertheless, obstacles including unwanted side effects due to the migration of transplanted cells as well as poor cell survival have remained unresolved. In order to overcome these problems, cell therapy has been introduced using biocompatible and biodegradable biomaterials to reduce cell loss and long-term in vitro retention of stem cells.
Currently in clinical trials, these biomaterials are widely used in drug and cell-delivery systems, regenerative medicine and tissue engineering in which to prevent the long-term survival of foreign substances in the body the release of cells are controlled (40).
Today, the incidence and prevalence of heart failure in human societies is a major and increasing problem that unfortunately has a poor prognosis. For decades, MSCs have been used for cardiovascular regenerative therapy as one of the potential therapeutic agents (41). Dhein et al. [2006] found that autologous bone marrow-derived mesenchymal stem cells (BMSCs) transplantation improves cardiac function in non-ischemic cardiomyopathy in a rabbit model. In one study, Davies et al. [2010] reported that transplantation of cord blood stem cells in ovine model of heart failure, enhanced the function of heart through improvement of right ventricular mass, both systolic and diastolic right heart function (42). In another study, Nagaya et al. [2005] found that MSCs dilated cardiomyopathy (DCM), possibly by inducing angiogenesis and preventing cardial fibrosis. MSCs have a tremendous beneficial effect in cell transplantation including in differentiating cardiomyocytes, vascular endothelial cells, and providing anti-apoptotic as well angiogenic mediators (43). Roura et al. [2015] shown that umbilical cord blood mesenchymal stem cells (UCBMSCs) are envisioned as attractive therapeutic candidates against human disorders progressing with vascular deficit (44). Ammar et al., [2015] compared BMSCs with adipose tissue-derived MSCs (ADSCs). It was demonstrated that both BMSCs and ADSCs were equally effective in mitigating doxorubicin-induced cardiac dysfunction through decreasing collagen deposition and promoting angiogenesis (45).
There are many advantages of small animal models usage in cardiovascular research compared with large animal models. Small model of animals has a short life span, which allow the researchers to follow the natural history of the disease at an accelerated pace. Some advantages and disadvantages are listed in (46).
Despite of the small animal model, large animal models are suitable models for studies of human diseases. Some advantages and disadvantages of using large animal models in a study protocol planning was elaborated in (47).
Chronic wound is one of the most common problem and causes significant distress to patients (48). Among the types of tissues that stem cells derived it, dental tissuederived MSCs provide good sources of cytokines and growth factors that promote wound healing. The results of previous studies showed that stem cells derived deciduous teeth of the horse might be a novel approach for wound care and might be applied in clinical treatment of non-healing wounds (49). However, the treatment with stem cells derived deciduous teeth needs more research to understand the underlying mechanisms of effective growth factors which contribute to the wound healing processes (50). This preliminary investigation suggests that deciduous teeth-derived stem cells have the potential to promote wound healing in rabbit excisional wound models (49). In the another study, Lin et al. [2013] worked on the mouse animal model and showed that ADSCs present a potentially viable matrix for full-thickness defect wound healing (51).
Many studies have been done on dental reconstruction with MSCs. In one study, Khorsand et al. [2013] reported that dental pulp-derived stem cells (DPSCs) could promote periodontal regeneration in canine model. Also, it was shown that canine DPSCs were successfully isolated and had the rapid proliferation and multi-lineage differentiation capacity (52). Other application of dental-derived stem cells is shown in .
Diagram for application of dental stem cell in dentistry/regenerative medicine (53).
As noted above, stem cells have different therapeutic applications and self-renewal capability. These cells can also differentiate into the different cell types. There is now a great hope that stem cells can be used to treat diseases such as Alzheimer, Parkinson and other serious diseases. In stem cell-based therapy, ESCs are essentially targeted to differentiate into functional neural cells. Today, a specific category of stem cells called induced pluripotent stem (iPS) cells are being used and tested to generate functional dopamine neurons for treating Parkinson's disease of a rat animal model. In addition, NSC as well as MSCs are being used in neurodegenerative disorder therapies for Alzheimers disease, Parkinsons disease, and stroke (54). Previous studies have shown that BMSCs could reduce brain amyloid deposition and accelerate the activation of microglia in an acutely induced Alzheimers disease in mouse animal model. Lee et al. [2009] reported that BMSCs can increase the number of activated microglia, which effective therapeutic vehicle to reduce A deposits in AD patients (55). In confirmation of previous study, Liu et al. [2015] showed that transplantation of BMSCs in brain of mouse model of Alzheimers disease cause to decrease in amyloid beta deposition, increase in brain-derived neurotrophic factor (BDNF) levels and improvements in social recognition (56). In addition of BMSCs, NSCs have been proposed as tools for treating neurodegeneration disease because of their capability to create an appropriate cell types which transplanted. kerud et al. [2001] demonstrated that NSCs efficiently express high level of glial cell line-derived neurotrophic factor (GDNF) in vivo, suggesting a use of these cells in the treatment of neurodegenerative disorders, including Parkinsons disease (57). In the following, Venkataramana et al. [2010] transplanted BMSCs into the sub lateral ventricular zones of seven Parkinsons disease patients and reported encouraging results (58).
The human body is fortified with specialized cells named MSCs, which has the ability to self-renew and differentiate into various cell types including, adipocyte, osteocyte, chondrocyte, neurons etc. In addition to mentioned properties, these cells can be easily isolated, safely transplanted to injured sites and have the immune regulatory properties. Numerous in vitro and in vivo studies in animal models have successfully demonstrated the potential of MSCs for various diseases; however, the clinical outcomes are not very encouraging. Based on the studies in the field of stem cells, MSCs find wide application in treatment of diseases, such as heart failure, wound healing, tooth regeneration and etc. In addition, these cells are particularly important in the treatment of the sub-branch neurodegenerative diseases like Alzheimer and Parkinson.
The authors wish to thank staff of the Stem Cell Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
Funding: The project described was supported by Grant Number IR.TBZMED.REC.1396.1218 from the Stem Cell Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.
Conflicts of Interest: The authors have no conflicts of interest to declare.
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Men With Arthritis Have Higher Fertility Rates, Study Finds Zenger.News
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Unveiling the Reality of Personalized Medicine: Yale Study Highlights Limitations in Current Predictive Models - Medriva
The question of how to live a long, healthy life is increasingly at the forefront of medical research. While centuries ago some may have turned to finding mythical immortality-granting items like the Holy Grail, scientists now say that achieving longevity may rely on eating the right foods, adopting healthy habits, and remaining socially active.
Reaching your hundredth birthday means you become a member of a special club of centenarians. While researchers believe the number of centenarians was very low before 1900, today many more people are able to reach this ripe old age.
As of 2021, there were an estimated 573,000 centenarians globally. The United Nations expects that number to jump rapidly, with a reported estimate of 3.7 million by 2050.
What do centenarians do to help them reach triple-digit birthdays what is their secret? Medical News Today spoke with six experts to find out what the secret sauce behind longevity is.
In 2016, National Geographic Fellow Dan Buettner and his team published a study on what they found to be the secrets to longevity.
Dubbed the Blue Zones, Buettner identified five specific areas of the world where people consistently live over 100 years of age. These areas are:
These are places where human beings have lived manifestly longest, Buettner explained to Medical News Today. Theyve achieved the health outcomes we want: long lives largely free of chronic disease. Since only 80% of how long we live is dictated by disease, these peoples lifestyles and environments offer us instructions and clues for how we can set up our lives to live longer.
Within these five areas, Buettner discovered there were nine common practices that people followed that might explain their slower aging process. Called the Power 9, they include:
Loneliness, said Buettner, is a top risk factor for a shorter life, so preventing that as much as we can could help add years to our lives:
We know that lonely people are expected to live 8 fewer years than well-connected people and that health behaviors [are] measurably contagious. People in Blue Zones are in socially connected villages with strong social ties, which gives them a longevity edge from the very beginning.
Theres no short-term fix [or] supplement for longevity, he added. Learn plant-based dishes that you like and cook at home. Curate a social circle of three to five healthy friends [who] will care about you on a bad day. Health behaviors are contagious, and friends tend to be long-term adventures.
As diet makes up a few of the Power 9 learned from Blue Zones, Buettner has also launched the Blue Zone Food Guidelines that feature 11 recommendations reflecting how the worlds longest-living people ate for most of their lives.
If you want to know what a centenarian [did to live] to be 100, you have to know what they ate during their whole [life], he said. Working with Harvard for my book The Blue Zones Kitchen, we collected 155 dietary studies done in all Blue Zones over the past 80 years and averaged them.
It was clear that over 90% of their traditional dietary intake came from whole food, plant-based sources [and] was about 65% complex carbs, noted Buettner. The pillars of every longevity diet in the world are whole grains, nuts, greens, and other garden vegetables, tubers, and beans.
Dr. Valter Longo, Edna M. Jones Chair in Gerontology and professor of gerontology and biological sciences at the USC Leonard Davis School of Gerontology, developed the Longevity Diet after years of research into aging, nutrition, and disease.
The Longevity Diet, based on [the] five pillars of longevity, entails all of the everyday and periodic dietary habits that are associated with increased longevity and healthspan, he explained to MNT.
The main facets of the Longevity Diet include:
Because diet [is] intended as how and what we eat and not as a method to lose weight, [it] can regulate the genes that regulate the aging process, but also those that regulate the removal of damaged components of cells and the regeneration of parts of various tissues and organs, Dr. Longo added.
Additionally, previous research suggests that the Mediterranean diet can also provide benefits when it comes to longevity.
A review published in January 2020 concluded that the Mediterranean diet helps slow down the progression of aging and the onset of frailty in older age.
And research published in March 2021 says adhering to the Mediterranean diet may add years to a persons life.
According to Monique Richard, a registered dietitian nutritionist, owner of Nutrition-In-Sight in Johnson City, TN, and national media spokesperson for the Academy of Nutrition and Dietetics, when it comes to eating for longevity, diets like the Blue Zone Diet, Longevity Diet, and Mediterranean diet stand out because of the lifestyle components they share.
Examples of commonalities observed within these populations include more families and individuals growing and consuming their food [and] eating more whole foods, as in closest to what Mother Nature has made versus derived from a manufacturing plant, industrial farm, or fast food chain, she explained to MNT.
Overall intake and composition of these diets include less highly-processed foods, therefore often automatically decreasing levels of sodium, artificial flavors, colorings, and preservatives, fats or added sugar. Richard noted.
These dietary patterns often include foods lower in saturated fats, cholesterol, and calories, including more foods that are richer in nutrients such as fiber, antioxidants like vitamin C, E, A, [and] B, and higher in minerals such as potassium, magnesium, and iodine.
Monique Richard
When looking to make diet changes to increase longevity, Richard said it is not just about extending life, but also about increasing its quality.
She suggested:
The emphasis is not on restriction or negative consequences, but leaning into true quality, consistency, and overall health with a pillar of foundational pure, wholesome factors, Richard said.
Dont forget to slow down with eating, with chewing, with making or creating a meal, with making time to stop and smell the flowers, [and] with making long-lasting meaningful changes, she added.
The power of positive thinking is known to be beneficial to a persons overall mental health. However, previous research shows that a positive attitude may even help a person live longer.
A study published in August 2019 found that being optimistic was associated with a person living 11-15% longer and having a stronger likelihood of living to age 85 or older.
Research published in October 2022 suggested that positive-thinking women in an ethnically diverse United States population lived an average of 4.4 years more than those who did not think positively.
Having a positive, optimistic outlook reduces our risk for developing chronic diseases and gives us a greater chance of living past 85, Dr. Karen D. Sullivan, a board-certified neuropsychologist and owner of I CARE FOR YOUR BRAIN in Pinehurst, NC explained to MNT.
The mechanism behind these benefits is thought to be related to the protection optimism offers against the inflammatory damage of stress. Studies on negative emotions show a weakening effect on the immune system.
Dr. Karen D. Sullivan
Additionally, Dr. Karen Miller, a neuropsychologist, geropsychologist, and senior director of the Brain Wellness and Lifestyle Programs at Pacific Neuroscience Institute in Santa Monica, CA, noted that inflammation caused by stress is one of the culprits leading to more rapid aging, more physical difficulties, and more cognitive difficulties.
So when were thinking positive and engaging in positive behaviors, such as [] meditation, yoga, participating in our own personal religious practices, getting out and walking, exercising, [or] enjoying the fresh air, all those things are bringing down our stress and bringing down our level of inflammation, she continued.
If were under a lot of stress were going to have higher inflammation and higher inflammation actually can cause cellular damage to our bodies, particularly our brains, Dr. Miller noted.
In addition to staying positive and participating in activities that help lower stress, remaining socially active and connected to other humans has also been associated with living a long life.
A study published in September 2019 found women who had strong social relationships had a 10% longer life span and 41% better chance of living to age 85.
And research published in May 2023 showed that frequent participation in social activity was significantly associated with prolonged overall survival in older adults.
We are social beings with a social brain we are wired to be part of a group with needs for both contributing value and being valued, Dr. Sullivan explained.
People who identify as lonely have a [] greater risk of dying early than those who feel satisfied with their social life. The chronic stress of loneliness weakens our immune systems, making us more susceptible to infectious diseases and chronic diseases, especially cardiovascular disease and cancer.
Dr. Karen D. Sullivan
When actively socializing, Dr. Miller said, we are engaging in cognitive stimulation that helps keep the brain engaged and healthy.
When we are involved with another person, there is that volley, that give and take, she told MNT. Its like a tennis match the ideas are going back and forth. And that type of cognitive stimulation actually inspires our brains to be more mentally agile, or like what we like to think of in neuropsychology as cognitive flexibility.
Plus, conversing and engaging with others helps you learn more information, think creatively, and stimulate problem-solving skills, resulting in what Dr. Miller referred to as a whole-brain workout.
That type of engagement, that social stimulation, is what I would call natures brain bootcamp, she added. Were literally engaging in bootcamp for our brain where were socializing, which is very different than if I was isolated and I didnt have that opportunity.
While experts agree a healthy diet, limiting stress, thinking positively, and staying socially active can potentially lead to a longer life, there are some other healthy habits that are also important.
For example, smoking can take years off your life. A study published in June 2020 found that not smoking and being socially engaged throughout older age were common in centenarians free from common chronic diseases.
Keeping a healthy weight is also important for longevity. Research published in 2017 concluded that a high body mass index (BMI) was associated with substantially shorter healthy and chronic disease-free life expectancy.
Regular exercise can also help you live longer. A study published in August 2022 found that light or moderate to vigorous physical activity were both associated with a lower risk of mortality in older women, while higher sedentary time increased their mortality risk.
Several studies have shown that physical activity is associated with lower risk of mortality in older adults, Dr. Aladdin Shadyab, associate professor of epidemiology at the Herbert Wertheim School of Public Health & Human Longevity Science at UC San Diego, and senior author of the study told MNT.
We were the first to show that higher levels of physical activity and lower time spent sedentary are associated with reduced risk of mortality, irrespective of having genes that predispose to a long life. These findings overall highlight the importance of maintaining a physically active lifestyle in old age to achieve longevity, said Dr. Shadyab.
I think maintaining a healthy diet and engaging in regular exercise is most important, particularly for older adults, he added. Even light activities, such as walking, are important for maintaining a long and healthy life in the aging population.
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Longevity: What lifestyle habits could help you live to 100?
Helen Mongelia's 102 years reflect the mysterious alchemy of genetic, environmental, and lifestyle factors that coalesce to aid longevity. Fresh food, consistent movement, emotional resilience, and a family full of long-living relatives mark the centenarian's colorful life span, which began in 1919 while Woodrow Wilson occupied the White House.
Longevity like Mrs. Mongelia's remains extraordinary, with an estimated one in 6,000 people in the United States reaching 100 nowadays, according to the U.S. Administration on Aging. More than 100,000 were 100 or older in 2019, triple the number in 1980 who'd passed their 100th birthday.
Scientists, including those at Harvard, are eagerly studying people in their 90s and beyond to tease out what contributes to exceptionally long living. People enduring to extreme old age often have lifestyles that fuel vigor and hamper age-related chronic diseases such as heart disease, cancer, and diabetes. They typically are nonsmokers, are not obese, and cope effectively with stress, according to the National Institutes of Health (NIH). Most are women.
"I didn't expect to live this long, that's for sure," says Mrs. Mongelia, who lived independently until 101 when she also gave up driving and happily holds a mailroom job at her assisted living residence in Connecticut. "But I've tried not to let anything bother me too much. I have two great daughters, two sons-in-law, and two grandchildren what else can you ask for? There's my happiness right there."
Mrs. Mongelia never restricted her diet, eating meat but skipping most alcoholic drinks. But her early fare as the middle child of 11 was abundant in fruits and vegetables, many grown in her family's garden in Carbondale, Pa., and canned to enjoy all year long. The large clan also walked "everywhere," trekking miles round-trip to church, school, and the grocery store.
Mrs. Mongelia's healthy habits hit a sweet spot that science increasingly spotlights as optimal for longevity. A new Harvard-led study spanning 11 years and involving 2,400 people (average age 60; 55% women) suggests that a Mediterranean diet rich in fruits, vegetables, and healthy fats may dampen inflammation and prevent age-related frailty, a major predictor of decline affecting between 10% and 15% of older adults.
"Frailty is hard to define, but it's really easy to spot. In general, it's a state of increased vulnerability," says Courtney Millar, a postdoctoral research fellow at the Marcus Institute for Aging Research at Harvard-affiliated Beth Israel Deaconess Medical Center.
"It's important to focus on frailty prevention and treatment, because it's associated with so many of the factors that determine someone's longevity," says Millar, a co-author of the study, published online May 12, 2022, by The American Journal of Clinical Nutrition.
Another new study suggests that young adults who begin optimizing their diets at age 20 by veering from typical Western fare to more whole grains, legumes, and nuts could increase their life expectancy by more than a decade. Published online Feb. 8, 2022, by PLOS Medicine, the study posited that people who start such dietary shifts even at age 60 can still reap substantial benefits, increasing life expectancy by eight years for women; 80-year-olds could gain another three-plus years.
"I'm certainly a believer that food is medicine," Millar says, "and there's some great evidence that dietary factors can improve longevity."
Mrs. Mongelia's family is peppered with relatives who've had far longer-than-average life spans. Although her coal miner father died of black lung disease at 78, Mrs. Mongelia's mother lived to 93, and many siblings also thrived into their 10th decade. Two brothers still survive.
Research reinforces this link: siblings and children of long-living people are more likely to live beyond peers and remain healthier while doing so, according to the NIH. A study published online May 28, 2022, by The Journals of Gerontology, Series A: Biological Sciences and Medical Sciences suggested that children of those who reach 100 carry a specific "genetic footprint" explaining why they're less frail than peers whose parents were not centenarians.
Might our genes be the linchpin to longevity? "My take is that it's certainly a combination of lifestyle and genetics," Millar says. "Certain dietary factors and even exercise regimens can modify how our genes are expressed and contribute to what's going on in our bodies. It's a really important intersection of our health."
Some scientists use the term "biohacks" to refer to tweaks in daily habits and choices that aim to tamp down inflammation and blunt aging's effects. Many of these tactics aren't new, but Harvard experts say that employing them consistently might contribute to longevity.
Move more. Vigorous movement has repeatedly been linked with lower risks of heart disease, diabetes, obesity, and other chronic health problems.
Review your health history. Talk to your primary care doctor about your health conditions and any new symptoms so you can manage them appropriately.
Try intermittent fasting. Compressing meals into a six- or eight-hour window each day boosts the body's natural process of eliminating damaged cells and proteins, lowering inflammation levels.
Eat a plant-forward diet. Antioxidants from fruits and vegetables and fiber from whole grains all help to lower inflammation levels. Beans, chickpeas, and other legumes were hailed as a key dietary predictor of longevity in a study that found a daily dietary increase of just 20 grams (less than an ounce) of legumes lowers our risk of dying in any given year by 8%.
Boost your outlook. List your life goals and imagine a future where they've been reached, or think about three good things that happened to you every day. Write them down.
Despite a hardscrabble path that included dropping out of school after 11th grade to take care of a baby sibling and also working as a button operator in a dress factory where she earned three cents per dozen buttons mounted Mrs. Mongelia maintains an upbeat attitude that matches her hardy body. She relies on a walker and hearing aids, but remains mentally sharp. "Just keep going and going and going, and don't give up," she counsels.
A recent Harvard-led analysis of nearly 160,000 American women linked positive outlook to extended life span. Published online June 8, 2022, by the Journal of the American Geriatrics Society, the study analyzed data and survey responses from women who were 50 to 79 years old when they enrolled in the study in the 1990s. The researchers then tracked participants' survival for up to 26 years. The results suggested that higher levels of optimism correlated with higher odds of living beyond 90.
About a quarter of the relationship between optimism and living longer may reflect health-related factors such as eating healthy foods, controlling weight, exercising, and limiting alcohol, says study co-author Dr. Hayami Koga, a researcher and doctoral candidate in population health sciences at the Harvard T.H. Chan School of Public Health.
The findings hint at the value of focusing on positive psychological factors as possible new ways of promoting longevity and healthy aging, Dr. Koga says. "There's some evidence that optimistic people are more likely to have goals and the confidence to reach them," she adds. "I think it drives people to be more confident and take actions that lead to better health."
Photo by Timothy H. Cole
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Environmental stress rather than genetics influenced height differences in early Neolithic people: Study - Phys.org