There are many ways in which human stem cells can be used in research and the clinic. Studies of human embryonic stem cells will yield information about the complex events that occur during human development. A primary goal of this work is to identify how undifferentiated stem cells become the differentiated cells that form the tissues and organs. Scientists know that turning genes on and off is central to this process. Some of the most serious medical conditions, such as cancer and birth defects, are due to abnormal cell division and differentiation. A more complete understanding of the genetic and molecular controls of these processes may yield information about how such diseases arise and suggest new strategies for therapy. Predictably controlling cell proliferation and differentiation requires additional basic research on the molecular and genetic signals that regulate cell division and specialization. While recent developments with iPS cells suggest some of the specific factors that may be involved, techniques must be devised to introduce these factors safely into the cells and control the processes that are induced by these factors.

Human stem cells are currently being used to test new drugs. New medications are tested for safety on differentiated cells generated from human pluripotent cell lines. Other kinds of cell lines have a long history of being used in this way. Cancer cell lines, for example, are used to screen potential anti-tumor drugs. The availability of pluripotent stem cells would allow drug testing in a wider range of cell types. However, to screen drugs effectively, the conditions must be identical when comparing different drugs. Therefore, scientists must be able to precisely control the differentiation of stem cells into the specific cell type on which drugs will be tested. For some cell types and tissues, current knowledge of the signals controlling differentiation falls short of being able to mimic these conditions precisely to generate pure populations of differentiated cells for each drug being tested.

Perhaps the most important potential application of human stem cells is the generation of cells and tissues that could be used for cell-based therapies. Today, donated organs and tissues are often used to replace ailing or destroyed tissue, but the need for transplantable tissues and organs far outweighs the available supply. Stem cells, directed to differentiate into specific cell types, offer the possibility of a renewable source of replacement cells and tissues to treat diseases including maculardegeneration, spinal cord injury, stroke, burns, heart disease, diabetes, osteoarthritis, and rheumatoid arthritis.

Figure 3. Strategies to repair heart muscle with adult stem cells. Click here for larger image.

2008 Terese Winslow

For example, it may become possible to generate healthy heart muscle cells in the laboratory and then transplant those cells into patients with chronic heart disease. Preliminary research in mice and other animals indicates that bone marrow stromal cells, transplanted into a damaged heart, can have beneficial effects. Whether these cells can generate heart muscle cells or stimulate the growth of new blood vessels that repopulate the heart tissue, or help via some other mechanism is actively under investigation. For example, injected cells may accomplish repair by secreting growth factors, rather than actually incorporating into the heart. Promising results from animal studies have served as the basis for a small number of exploratory studies in humans (for discussion, see call-out box, "Can Stem Cells Mend a Broken Heart?"). Other recent studies in cell culture systems indicate that it may be possible to direct the differentiation of embryonic stem cells or adult bone marrow cells into heart muscle cells (Figure 3).

Cardiovascular disease (CVD), which includes hypertension, coronary heart disease, stroke, and congestive heart failure, has ranked as the number one cause of death in the United States every year since 1900 except 1918, when the nation struggled with an influenza epidemic. Nearly 2,600 Americans die of CVD each day, roughly one person every 34 seconds. Given the aging of the population and the relatively dramatic recent increases in the prevalence of cardiovascular risk factors such as obesity and type 2 diabetes, CVD will be a significant health concern well into the 21st century.

Cardiovascular disease can deprive heart tissue of oxygen, thereby killing cardiac muscle cells (cardiomyocytes). This loss triggers a cascade of detrimental events, including formation of scar tissue, an overload of blood flow and pressure capacity, the overstretching of viable cardiac cells attempting to sustain cardiac output, leading to heart failure, and eventual death. Restoring damaged heart muscle tissue, through repair or regeneration, is therefore a potentially new strategy to treat heart failure.

The use of embryonic and adult-derived stem cells for cardiac repair is an active area of research. A number of stem cell types, including embryonic stem (ES) cells, cardiac stem cells that naturally reside within the heart, myoblasts (muscle stem cells), adult bone marrow-derived cells including mesenchymal cells (bone marrow-derived cells that give rise to tissues such as muscle, bone, tendons, ligaments, and adipose tissue), endothelial progenitor cells (cells that give rise to the endothelium, the interior lining of blood vessels), and umbilical cord blood cells, have been investigated as possible sources for regenerating damaged heart tissue. All have been explored in mouse or rat models, and some have been tested in larger animal models, such as pigs.

A few small studies have also been carried out in humans, usually in patients who are undergoing open-heart surgery. Several of these 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. The mechanism for this repair remains controversial, and the stem cells likely regenerate heart tissue through several pathways. However, the stem cell populations that have been tested in these experiments vary widely, as do the conditions of their purification and application. Although much more research is needed to assess the safety and improve the efficacy of this approach, these preliminary clinical experiments show how stem cells may one day be used to repair damaged heart tissue, thereby reducing the burden of cardiovascular disease.

In people who suffer from type1 diabetes, the cells of the pancreas that normally produce insulin are destroyed by the patient's own immune system. New studies indicate that it may be possible to direct the differentiation of human embryonic stem cells in cell culture to form insulin-producing cells that eventually could be used in transplantation therapy for persons with diabetes.

To realize the promise of novel cell-based therapies for such pervasive and debilitating diseases, scientists must be able to manipulate stem cells so that they possess the necessary characteristics for successful differentiation, transplantation, and engraftment. The following is a list of steps in successful cell-based treatments that scientists will have to learn to control to bring such treatments to the clinic. To be useful for transplant purposes, stem cells must be reproducibly made to:

Also, to avoid the problem of immune rejection, scientists are experimenting with different research strategies to generate tissues that will not be rejected.

To summarize, stem cells offer exciting promise for future therapies, but significant technical hurdles remain that will only be overcome through years of intensive research.

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Adult stem cells are the bodys toolbox, called into action by normal wear and tear on the body, and when serious damage or disease attack. Researchers believe that adult stem cells also have the potential, as yet untapped, to be tools in medicine. Scientists and physicians are working towards being able to treat patients with their own stem cells, or with banked donor stem cells that match them genetically.

Grown in large enough numbers in the lab, then transplanted into the patient, these cells could repair an injury or counter a diseaseproviding more insulin-producing cells for people with type 1 diabetes, for example, or cardiac muscle cells to help people recover from a heart attack. This approach is called regenerative medicine.

A number of challenges must be overcome before the full therapeutic potential of adult stem cells can be realized. Scientists are exploring practical ways of harvesting and maintaining most types of adult stem cells. Right now, scientists do not have the ability to grow the cells in the amounts needed for treatment. More work is also needed to find practical ways to direct the different kinds of cells to where theyre needed in the body, preferably without the need for surgery or other invasive methods.

Research in all aspects of adult stem cells and their potential is underway at Childrens Hospital Boston. Realizing that potential will require years of research, but promising strides are being made.

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Statistics indicate that approximately 17,500 people suffer spinal cord injuries each year. Although these injuries can impact anyone, they are most commonly seen in younger men, primarily because these injuries are often driven by lifestyle choices that people may make. Yet, despite efforts to more effectively treat these spinal cord injuries and restore full quality of life, traditional medical treatments have largely been unsuccessful.

Due to this fact, medical professionals have increasingly turned their attention to stem cells and how these stem cells could be used to treat spinal cord injuries.

In short, there is no way to reverse damage to the spinal cord that doesnt include replacing the old cells, like with stem cells. However, there are some treatment options available as to prevent the injury becoming worse, especially immediately during or after the injury event. With any luck, some patients can return to an active and normal life through these means without having to resort to stem cells, which is still a clinical and expensive treatment.

Most of what can be done for a spinal cord injury is at the scene. These require the patient to remain motionless in order to prevent shock. Immobilizing the neck and spinal cord can help reduce further injury and complications, not to mention maintaining steady breathing. Surgery is often necessary for this type of injury. Some medication, particularly methylprednisolone, can be used, but the side effects of blood clots and illness usually outweigh the benefits.

In the long run, doctors make a priority to prevent problems with other parts of the body as a result of spinal cord injuries. Blood clots, respiratory infections, pressure ulcers and other issues have been known to arise.

Otherwise, rehabilitation is almost always recommended to rebuild muscle strength while in the early stages of recovery. Education on how to prevent further complications in day-to-day life is also given to patients with these types of injuries, along with learning new skills to help through their new situation.

With treatment for spinal cord injuries being severely limited, there is little wonder why doctors and researchers have turned to the idea of using stem cells to rebuild and replace damaged cells. However, these stem cells cant just be injected in any traditional sense. They need to be placed accurately in an environment where they can grow. This is where 3D printing comes in.

Recognizing the fact that traditional treatment methods have not been able to fully improve patients quality of life, medical professionals are shifting their attention to exploring stem cells and how stem cells can improve functioning for individuals with spinal cord injuries. The pioneering study in this sphere came out of the University of California San Diegos School of Medicine and Institute of Engineering.

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Fight the signs of premature aging with these stem cell skin care beauty products. A lot of companies claim to incorporate the benefits of plant and human stem cells, as well as components secreted by them, into the best stem cell beauty products on the market. Below, we present what appears (based on company claims) to be ten of the best products available today.

As a publisher of stem cell news, we havent traditionally wandered into the world of claims made by stem cell beauty products suppliers. For obvious reasons, we cannot guarantee the accuracy of the claims made by these companies or the presence of specific active agents within them.

However, we get approached daily with questions about this topic and know that people are seeking information about it from a source that: 1) Doesnt inflate the claims, and 2) Understands the science.

For this reason, we have decided to share with you what appear to be interesting skin care options, coupled with a healthy dose of warnings reminding you that the stated claims may or may not be accurate.

Kimera Labs makes the top of this list for numerous reasons. First, the companys science it is solid. Instead of being a supplier of beauty products, the company is a specialty contract research organization (CRO) focusing on regenerative medicine applications, including exosome purification. Exosomes are small vesicles (~30-100nm) that are secreted by nearly all cell types and act as intracellular mail.

Exosomes transfer DNA, RNA, and proteins to other cells, thereby altering the function of the other cells.

Second, the company has an FDA registered tissue facility in Miami, FL, where it develops pharmaceutical grade, exosome-based regenerative therapies. The company has a 6,000 sq. ft. facility in Miramar, Florida, that includes impressive features such asISO:9001/13485 certification, cleanrooms, and a variety of high-end scientific equipment.

Third, the company is run by Dr. Duncan Ross, a highly regarded scientist with a Ph.D. in Immunology from the University of Miami. Dr. Ross is also a Principal at The Kimera Society, a non-profit organization dedicated to the advancementof stem cells, regenerative medicine,and cancer immunotherapies.

For those seeking stem cell beauty products, the companys core offering is XoGlo, a product which provides growth and healing signals to guide the re-deposition of tissue and avoid the scarring that often accompanies burns or other skin damage. You can see an incredible Case Study from the company in which XoGlo was used to heal second-degree burns in a patient in approximately seven days. The product can also be used for general skin health and enhancement.

More information on the XoGlois available here.

According to the company, this facial cleanser is formulated with stem cytokines that promote the skins ability to heal itself, leaving softer and smoother skin. It also has essential fatty acids, detoxifying actives, antioxidants, and anti-inflammatory botanicals that deeply cleanse your skin of excess oil, impurities, and surface debris. This makes the skin smoother, more balanced, and hydrated.

Lifeline says that it offers a moisture serum with a formula consisting of proteins and peptides from pluripotent stem cells. It works by reversing skin aging signs and actively moisturizing the skin with its cucumber melon extracts. The serum primarily targets the reduction of wrinkles and fine lines.

At $105 for a 1 oz bottle, it is notable that the company does not mention how it sources pluripotent stem cells, leaving key questions about its active ingredients unanswered.

Heres another skin care serum on this list of stem cellbeauty products. This serum is enriched with a tissue nutrient solution (TNS) technology that reduces wrinkles and fine lines and improves skin texture and tone. TNS is formulated with matrix proteins, cytokines, soluble collagen, antioxidants, and growth factors that are essential to keeping skin healthy.

This regenerative eye creamcontains autokine-CM obtained from adult stem cells through mini-liposuction. This unique ingredient is composed of extracted cytokines, matrix proteins, and growth factors from adult stem cells that help improve the skins ability to heal. It also aids in synthesizing elastin and collagen production, thus reducing fine lines and wrinkles, improving skin tone and texture, and increasing epidermal thickness in the eye area.

Venus Skin introduced a stem cell therapy serum packed with bio-signals from bone marrow mesenchymal stem cells for stimulation of skin tissue repair and healing. This reverses aging signs and rejuvenates the feel and look of the skin. It also contains essential vitamins A, C, and E to normalize skin functions, promote collagen synthesis in the skin, and reduce the appearance of scars, respectively.

This hydrating mask possesses a stem cell culture technology that penetrates deep into the skin for intense and long-lasting hydration. This leaves the skin well-moisturized and supple. It also fills fine lines and wrinkles and restores parched skin, bringing skin moisture and smoothness back.

This intensive facial mist restores the skins elasticity and moisture with its fine liquid particles that immediately penetrate the skin. It contains APL stem cell-conditioned medium extracts that help regenerate, whiten, and hydrate the skin and minimize pores and wrinkles. The facial mist also has chamomile extracts that bring a soothing effect to the skin.

Skin Drink Phytoceuticals highlights three potent anti-aging skin care ingredients in this serum.PhytoCellTec is an ingredient that safeguards the skin stem cells longevity, fights off skin aging, and delays biological aging of cells. Derm SRC works on reducing wrinkles and fine lines, while Ellagi-C promotes skin elasticity and suppleness.

This snail serum boasts an epidermal growth factor ingredient that stimulates the skins stem cell growth and cell survival. It also has a snail mucus extract that refreshes and brightens the skin. Aside from that, the serum contains other natural ingredients, such as macadamia seed oil and hydrolyzed placenta extract, for skin hydration and nourishment.

Which of these components actually enhance skin health and complexion? Hard to say, but the ingredient list certainly is exotic.

With this list of the best beauty products, it can be tricky to know which ones will enhance skin health. Stem cells are becoming a common ingredient in skin products, but regulation of this area is sparse, making it important to be vigilant in your selection.

A steep price tag doesnt guarantee results. Claims of active ingredients do not guarantee they are present. Even the confirmed presence of an ingredient by third-party testing does not substantiate its claimed effect.

However, there are hundreds of user reviews for some of these products, so the possibility for these skin care products to improve the appearance of your skin does exist. Importantly, many of these stem cell beauty products contain an impressive range of other ingredients, so you could benefit from them due to effects unrelated to the claimed stem cell components.

When judging the efficacy of these products, the only clear answer is that you need to be your own study of one.

If you found this article valuable, subscribe to BioInformantsstem cell industry updates.We are the industry leaders in stem cell research, with research cited byThe Wall Street Journal, Xconomy, AABB, andVogue Magazine.Bringing you breaking news on an ongoing basis, join more than half a million loyal readers, including physicians, scientists, executives, investors,and philanthropists.

Let this infographic be your guide. Download it now and use it as a reference later.

10 Best Stem Cell Beauty Products On The Market Today

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Stem cells in menstrual blood have similar regenerative capabilities as thestem cells in umbilical cord blood and bone marrow. Cryo-Cell's patent-pendingmenstrual stem cell service offers women in their reproductive years the ability to store and preserve these cells for potential use by herself or a family memberfree from ethical or political controversy.

Cryo-Cell is the only stem cell bank in the world that can offer womenthe reassurance and peace of mind that comes with this opportunity.

What are menstrual stem cells?Stem cells in menstrual blood are highly proliferativeandpossess the unique ability to develop into various other types of healthy cells. During a womans menstrual cycle, these valuable stem cells are discarded.

Cryo-Cell'smenstrual stem cell bankingservice captures those self-renewing stem cells, processes and cryopreserves them for emerging cellular therapies that hold the promise of potentially treatinglife-threatening diseases.

How are menstrual stem cells collected, processed and stored?The menstrual blood is collected in a physicians officeusing a medical-grade silicone cup in place of a tampon orsanitary napkin. The sample is shipped to Cryo-Cell via a medical courier and processed in our state-of-the-art ISO Class 7 clean room.

The menstrual stem cells are stored in two cryovials that are overwrapped to safeguard them during storage. The overwrapped vials are cryogenically preserved in a facility that isclosely monitored at all times to ensure that your menstrual stem cells are safe and ready for future use.

What are the benefits of banking menstrual stem cells?Cryo-Cell's innovative menstrual stem cell banking service provides women with the exclusive opportunity to build their own personal healthcare portfolio with stem cells that will be a 100% match for the donor. Menstrual stem cells have demonstrated the capability of differentiating into many other types of stem cells such as cardiac, neural, bone, fat and cartilage.

Bankingmenstrual stem cells now is an investment in your future medical needs. Currently, they are being studied to treat stroke, heart disease, diabetes, neurodegenerative disease, and ischemic wounds in pre-clinical and clinical models.

Cryo-Cells activities for New York State residents are limited to collection, processing, and long-term storage ofmenstrual stem cells. Cryo-Cells possession of a New York State license for such collection, processing, and long-term storage does not indicate approval or endorsement of possible future uses or future suitability of these cells.

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Presented At:Gibco - 24 Hours of Stem Cells Virtual Event

Presented By:Kapil Bharti - Stadtman Investigator, NIH, Unit on Ocular Stem Cell & Translational Research

Speaker Biography:Dr. Kapil Bharti holds a bachelor's degree in Biophysics from the Panjab University, Chandigarh, India, a master's degree in biotechnology from the M.S. Rao University, Baroda, India, and a diploma in molecular cell biology from Johann Wolfgang Goethe University, Frankfurt, Germany. He obtained his Ph.D. from the same institution, graduating summa cum laude. His Ph.D. work involved research in the areas of heat stress, chaperones, and epigenetics.

Webinar:Autologous iPS cell therapy for Macular Degeneration: From bench-to-bedside

Webinar Abstract:Induced pluripotent stem (iPS) cells are a promising source of personalized therapy. These cells can provide immune-compatible autologous replacement tissue for the treatment of potentially all degenerative diseases. We are preparing a phase I clinical trial using iPS cell derived ocular tissue to treat age-related macular degeneration (AMD), one of the leading blinding diseases in the US. AMD is caused by the progressive degeneration of retinal pigment epithelium (RPE), a monolayer tissue that maintains vision by maintaining photoreceptor function and survival. Combining developmental biology with tissue engineering we have developed clinical-grade iPS cell derived RPE-patch on a biodegradable scaffold. This patch performs key RPE functions like phagocytosis of photoreceptor outer segments, ability to transport water from apical to basal side, and the ability to secrete cytokines in a polarized fashion. We confirmed the safety and efficacy of this replacement patch in animal models as part of a Phase I Investigational New Drug (IND)-application. Approval of this IND application will lead to transplantation of autologous iPS cell derived RPE-patch in patients with the advanced stage of AMD. Success of NEI autologous cell therapy project will help leverage other iPS cell-based trials making personalized cell therapy a common medical practice.

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When the healthy stem cells come from you, the procedure is called an autologous transplant. When the stem cells come from another person, called a donor, it is an allogeneic transplant. Blood or bone marrow transplants most commonly are used to treat blood cancers or other kinds of blood diseases that decrease the number of healthy blood cells in the body. These transplants also may be used to treat other disorders.

For allogeneic transplants, your doctor will try to find a donor whose blood cells are the best match for you. Your doctor will consider using cells from your close family members, from people who are not related to you and who have registered with the National Marrow Donor Program, or from publicly stored umbilical cord blood. Although it is best to find a donor who is an exact match to you, new transplant procedures are making it possible to use donors who are not an exact match.

Blood or bone marrow transplants are usually performed in a hospital. Often, you must stay in the hospital for one to two weeks before the transplant to prepare. During this time, you will have a narrow tube placed in one of your large veins. You may be given medicine to make you sleepy for this procedure. You also will receive special medicines and possibly radiation to destroy your abnormal stem cells and to weaken your immune system so that it wont reject the donor cells after the transplant.

On the day of the transplant, you will be awake and may get medicine to relax you during the procedure. The stem cells will be given to you through the narrow tube in your vein. The stem cells will travel through your blood to your bone marrow, where they will begin making new healthy blood cells.

After the transplant, your doctor will check your blood counts every day to see if new blood cells have started to grow in your bone marrow. Depending on the type of transplant, you may be able to leave, but stay near the hospital, or you may need to remain in the hospital for weeks or months. The length of time will depend on how your immune system is recovering and whether or not the transplanted cells stay in your body. Before you leave the hospital, the doctors will give you detailed instructions that you must follow to prevent infection and other complications. Your doctor will keep monitoring your recovery, possibly for up to oneyear.

Although blood or bone marrow transplant is an effective treatment for some conditions, the procedure can cause early or late complications. The required medicines and radiation can cause nausea, vomiting, diarrhea, tiredness, mouth sores, skin rashes, hair loss, or liver damage. These treatments also can weaken your immune system and increase your risk for infection. Some people may experience a serious complication called graft-versus-host disease if the donated stem cells attack the body. Other people may reject the donor stem cells after the transplant, which can be an extremely serious complication.

VisitBlood-Forming Stem Cell Transplantsfor more information about this topic.

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Sossi, V., Holden, J. E., de la Fuente-Fernandez, R., Ruth, T. J. & Stoessl, A. J. Effect of dopamine loss and the metabolite 3-O-methyl-[18F]fluoro-dopa on the relation between the 18F-fluorodopa tissue input uptake rate constant Kocc and the [18F]fluorodopa plasma input uptake rate constantKi. J. Cereb. Blood Flow Metab. 23, 301309 (2003)

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Stromal vascular fraction was dramatically better than bone marrow concentrate in its ability to differentiate into cartilage.Two other important features were also well documented in this study. SVF created significantly more colony forming units than BMC, another significant predictor of healing response. Perhaps most importantly, SVF was dramatically better than BMC in its ability to differentiate into cartilage.

Second, a study by Han Chao et al has also demonstrated that fat derived stem cells also have a higher proliferation potential for neural tissue and are a better source for not only cartilage regeneration but also for nervous system regeneration.

The studies gave a very comprehensive look at comparing BMC and SVF in the ability to repair cartilage damage in a same procedure protocol. Every significant measurement comparing bone marrow to adipose tissue for stem cell harvesting demonstrated that adipose derived stem cells provided better cell content and superior ability to differentiate into cartilage than bone marrow. Our extensive clinical experience with the procedure for Colorado patients suffering from pain in the knees, other joints, soft tissue, and a wide range of back problems clearly demonstrates the same.

Using the most effective combination of autologous stem cell sources is one of several criteria to identify a legitimate stem cell clinic. Other important characteristics we recommend paying attention to when choosing a stem cell clinic, include the presence of a physician who owns and operates the clinic, X-ray guided injections administered by a trained injection specialist, and a clinic that takes time to discuss your questions. A review of your imaging and clinical data is needed in order to determine if stem cell therapy is right for you.

*Individual patient results may vary. Contact us today to find out if stem cell therapy may be able to help you.

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Bellin, M., Marchetto, M. C., Gage, F. H. & Mummery, C. L. Induced pluripotent stem cells: the new patient? Nat. Rev. Mol. Cell Biol. 13, 713726 (2012).

Matsa, E., Burridge, P. W. & Wu, J. C. Human stem cells for modeling heart disease and for drug discovery. Sci. Transl. Med. 6, 239 (2014).

Wang, G. et al. Modeling the mitochondrial cardiomyopathy of Barth syndrome with induced pluripotent stem cell and heart-on-chip technologies. Nat. Med. 20, 616623 (2014).

Yazawa, M. et al. Using induced pluripotent stem cells to investigate cardiac phenotypes in Timothy syndrome. Nature 471, 230234 (2011).

Yang, X., Pabon, L. & Murry, C. E. Engineering adolescence: maturation of human pluripotent stem cell-derived cardiomyocytes. Circ. Res. 114, 511523 (2014).

Feric, N. T. & Radisic, M. Maturing human pluripotent stem cell-derived cardiomyocytes in human engineered cardiac tissues. Adv. Drug Deliv. Rev. 96, 110134 (2016).

Domian, I. J. et al. Generation of functional ventricular heart muscle from mouse ventricular progenitor cells. Science 326, 426429 (2009).

Lundy, S. D., Zhu, W. Z., Regnier, M. & Laflamme, M. A. Structural and functional maturation of cardiomyocytes derived from human pluripotent stem cells. Stem Cells Dev. 22, 19912002 (2013).

Nunes, S. S. et al. Biowire: a platform for maturation of human pluripotent stem cell-derived cardiomyocytes. Nat. Methods 10, 781787 (2013).

Mannhardt, I. et al. Human engineered heart tissue: analysis of contractile force. Stem Cell Reports 7, 2942 (2016).

Ribeiro, M. C. et al. Functional maturation of human pluripotent stem cell derived cardiomyocytes in vitrocorrelation between contraction force and electrophysiology. Biomaterials 51, 138150 (2015).

Shadrin, I. Y. et al. Cardiopatch platform enables maturation and scale-up of human pluripotent stem cell-derived engineered heart tissues. Nat. Commun. 8, 1825 (2017).

Brette, F. & Orchard, C. T-tubule function in mammalian cardiac myocytes. Circ. Res. 92, 11821192 (2003).

Wiegerinck, R. F. et al. Force frequency relationship of the human ventricle increases during early postnatal development. Pediatr. Res. 65, 414419 (2009).

Lopaschuk, G. D. & Jaswal, J. S. Energy metabolic phenotype of the cardiomyocyte during development, differentiation, and postnatal maturation. J. Cardiovasc. Pharmacol. 56, 130140 (2010).

Jackman, C. P., Carlson, A. L. & Bursac, N. Dynamic culture yields engineered myocardium with near-adult functional output. Biomaterials 111, 6679 (2016).

Radisic, M. et al. Functional assembly of engineered myocardium by electrical stimulation of cardiac myocytes cultured on scaffolds. Proc. Natl Acad. Sci. USA 101, 1812918134 (2004).

Eng, G. et al. Autonomous beating rate adaptation in human stem cell-derived cardiomyocytes. Nat. Commun. 7, 10312 (2016).

Hasenfuss, G. et al. Energetics of isometric force development in control and volume-overload human myocardium. Comparison with animal species. Circ. Res. 68, 836846 (1991).

Chung, S. et al. Mitochondrial oxidative metabolism is required for the cardiac differentiation of stem cells. Nat. Clin. Pract. Cardiovasc. Med. 4, S60S67 (2007).

Gong, G. et al. Parkin-mediated mitophagy directs perinatal cardiac metabolic maturation in mice. Science 350, aad2459 (2015).

Porter, G. A. Jr et al. Bioenergetics, mitochondria, and cardiac myocyte differentiation. Prog. Pediatr. Cardiol. 31, 7581 (2011).

Vega, R. B., Horton, J. L. & Kelly, D. P. Maintaining ancient organelles: mitochondrial biogenesis and maturation. Circ. Res. 116, 18201834 (2015).

Gottlieb, R. A. & Bernstein, D. Metabolism. Mitochondria shape cardiac metabolism. Science 350, 11621163 (2015).

Sun, R., Bouchard, M. B. & Hillman, E. M. C. SPLASSH: Open source software for camera-based high-speed, multispectral in-vivo optical image acquisition. Biomed. Opt. Express 1, 385397 (2010).

Hong, T. et al. Cardiac BIN1 folds T-tubule membrane, controlling ion flux and limiting arrhythmia. Nat. Med. 20, 624632 (2014).

Bers, D. M. Cardiac excitationcontraction coupling. Nature 415, 198205 (2002).

Huebsch, N. et al. Miniaturized iPS-cell-derived cardiac muscles for physiologically relevant drug response analyses. Sci. Rep. 6, 24726 (2016).

Tulloch, N. L. et al. Growth of engineered human myocardium with mechanical loading and vascular coculture. Circ. Res. 109, 4759 (2011).

Ma, J. et al. High purity human-induced pluripotent stem cell-derived cardiomyocytes: electrophysiological properties of action potentials and ionic currents. Am. J. Physiol. Heart Circ. Physiol. 301, H2006H2017 (2011).

Morikawa, K., Song, L., Ronaldson-Bouchard, K., Vunjak-Novakovic, G. & Yazawa, M. Electrophysiological recordings of cardiomyocytes isolated from engineered human cardiac tissues derived from pluripotent stem cells.Protoc. Exch. https://doi.org/10.1038/protex.2018.030 (2018).

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At the turn of the century, prevailing dogma stated that the adult mammalian heart was incapable of self-repair. Postnatal growth reflected increases in cardiomyocyte size alone rather than through increases in cell number. This dogma was shaken by the demonstration that bone marrow cells could be used to regenerate heart muscle. The subsequent discovery that adult hearts contained cells that expressed the haematological stem cell marker c-Kit led to a large body of literature, mostly from Piero Aversas laboratory, which advanced the premise that cardiac c-Kit+ cells were clonogenic, multipotent, and capable of self-renewal (i.e. genuine heart stem cells). While this hypothesis was popularized and espoused by many, the validity of Anversas findings were questioned early on by several investigators who failed to reproduce key findings.1,2

On 14 October 2018, the Harvard Medical School and Brigham and Womens Hospital brought an end to this chapter as 31 papers from the lab pioneering heart c-Kit+ cells were recommended for retraction because the validity of the scientific data was uncertain. While the full identity of the papers affected is still unknown, the New England Journal of Medicine promptly issued an expression of concern that the data presented in two (heretofore) landmark papers in cardiac regeneration may not be reliable3 and outright retracted a 2011 paper demonstrating evidence for human lung c-Kit+ stem cells.4

On the heels of multiple corrections,511 institutional settlements,12 lawsuits,13 and prior retractions,14 it appears much of the literature supporting resident (in situ) c-Kit+ cells having any role in cardiac repair is open to question. The impact of this verdict is only now starting to be understood and has led many to question the concept of heart stem cells in the post-Anversa era.

Yes. Archaeological carbon-14 dating conclusively established that half of all cardiomyocytes are renewed over an individual lifespan.15 This repopulation decreases with advanced years. For example, at 25years old almost 1% of cardiomyocytes turn-over every year compared with only 0.5% turnover after 75years. Such numberslow but definitely not zerohave been confirmed by others using complementary methods in experimental animals.16,17

No. Reports began to emerge 10years ago questioning the cardiomyogenic potential of c-Kit+ cells.1820 Recent lineage tracking from multiple labs using complimentary techniques has established that endogenous cardiac c-Kit+ cells do not generate cardiomyocytes.2123

Probably not. Early reports panned through tissue lysate and heart sections for cells expressing embryonic or haematological stem markers in hopes of identifying cells that could be enticed to express cardiac markers in culture. In the absence of lineage tracking, the origin of the cells discovered is uncertain and very well may represent extra-cardiac contamination. It follows that cardio myogenesis seen before or after injury likely arises from myocardial de-differentiation only.24 Although cardiosphere-derived cells (CDCs) are clonogenic and multipotent in vitro,25 they have long been recognized not to function as cardiac progenitors after transplantation in vivo.26

In 2004, Messina et al. demonstrated a mixed population of CD105+ CD45-cells, explant-derived cells that spontaneously emigrate from heart tissue plated in culture.27 Forensic analysis showed these cells are intrinsically cardiac with no detectable seeding from extra-cardiac organs.28 To enable cell expansion to clinical doses, explant-derived cells have been antigenically selected or sphere cultured to generate c-Kit+ cells or CDCs, respectively (see Figure1). Independent labs have shown that both c-Kit+ cells (6 labs) or CDCs (45+ labs) improve heart function when delivered after injury. Unfortunately, studies providing direct comparisons between either cell type are often difficult to interpret as divergent cell culture methods or patient comorbidities influence cell potency; however, within CDCs, the small c-Kit+ cell fraction does not contribute to and is not necessary for, the observed gains in function.29

Figure 1

Schematic outline of heart-derived cell therapeutic manufacturing and identity. Explant-derived cells are cultured from myocardial tissue for antigenic selection (c-Kit+ cells, left panels) or sphere culture (CDCs, right panels) prior to expansion. Representative c-Kit+ cell images demonstrate freshly isolated human c-Kit+ cells (left panel, black dots, beads from magnetic-activated cell sorting) and during cell expansion (right panel, low confluence to highlight cell morphology). Representative images of CDCs cultured from transgenic mouse tissue expressing the c-Kit reporter (green fluorescent protein)18 highlighting the proportion of c-Kit+ cells within. Also shown is flow cytometry characterization from the SCIPIO (c-Kit+ cell trial, left panel)35 and CADUCEUS (CDC trial, right panel)41 trials contrasting the antigenic identity of each heart-derived cell therapeutic used in clinical trials.

Figure 1

Schematic outline of heart-derived cell therapeutic manufacturing and identity. Explant-derived cells are cultured from myocardial tissue for antigenic selection (c-Kit+ cells, left panels) or sphere culture (CDCs, right panels) prior to expansion. Representative c-Kit+ cell images demonstrate freshly isolated human c-Kit+ cells (left panel, black dots, beads from magnetic-activated cell sorting) and during cell expansion (right panel, low confluence to highlight cell morphology). Representative images of CDCs cultured from transgenic mouse tissue expressing the c-Kit reporter (green fluorescent protein)18 highlighting the proportion of c-Kit+ cells within. Also shown is flow cytometry characterization from the SCIPIO (c-Kit+ cell trial, left panel)35 and CADUCEUS (CDC trial, right panel)41 trials contrasting the antigenic identity of each heart-derived cell therapeutic used in clinical trials.

Not as much as we thought! Ex vivo expanded c-Kit+ cells were inspired by the Anversa literature and it was thought, until recently, that robust cell numbers persisted for many years after intramyocardial injection.30 The in situ c-Kit+ cell findings, which largely emanated from the well-funded Anversa lab, were directly extended to ex vivo expanded c-Kit+ cells. Since then, it has been concretely established that few transplanted cells engraft beyond a few days.31 This surprising observation revealed that c-Kit+ cells were evanescent, and thus not functioning as stem cells.

This realization came very late for c-Kit+ cells, unlike CDCs, which have been known for >10years to be effective despite little persistence of injected cells beyond 4weeks (i.e. 23% of the initial injectate).32,33 Fortunately, the CDC literature provides a clear template for these investigations with several articles listing comprehensive proteomic analysis, cytokine over-expression/subtraction data supporting causation, exosome profiling data and microRNA addition/subtraction data supporting a causative role in post infarct repair.34

Although very late in the game, a great deal of the basic phenotyping work is not yet known about c-Kit+ cells; including the fundamental differences between heart-derived and extra-cardiac c-Kit+ cells. It may be that c-Kit+ cells stimulate many of the immunomodulatory (macrophage polarization) and trophic (angiogenic, anti-apoptotic, mitotic and anti-scarring) endogenous repair mechanisms already identified in the CDC literature but much waits to be uncovered.

Reports of their death have been greatly exaggerated. The 2011 Phase 1 SCIPIO Trial demonstrated intra-coronary injection of c-Kit+ cells was safe and provided encouraging hints of efficacy as shown by increases in cardiac ejection fraction, New York Heart Association (NYHA) class and viable myocardium.35 But the subsequent 2014 expression of concern by The Lancet36 reflected cell product characterization, identity and manufacturing which were both done in Boston by Dr Anversas team.37 The impact of recent events on interpretation of the SCIPIO Trial is still not known but may emerge as the journals affected by the list of articles recommended for retraction receive more information.

The CONCERT HF Trial (ClinicalTrials.gov Identifier: NCT02501811) began in 2015 to explore the effects of combining heart-derived c-Kit+ cells with blood mesenchymal stem cells on post infarct repair.38 This trial was based upon two preclinical studies suggesting combined therapy increases transplanted cell engraftment to enhance cell treatment outcomes.39,40 With the Harvard c-Kit+ cell retractions, the NIHBLI paused the trial on 29 October 2018 to provide the Data and Safety Monitoring Board (DSMB) an opportunity to review the literature supporting the scientific foundations of the trial. Given the invasive nature of the trial (and the observation that a patient died during endomyocardial biopsy), this caution is appreciated to ensure that sufficient pre-clinical insight and clinical equipoise still exist in the new post-Anversa era.

At best, the future of heart c-Kit+ cells is uncertain. With the astounding number of key publications likely to be retracted, it may very well be that adult c-Kit+ cells are not fundamentally different enough from other heart-derived cells to warrant efforts exploring clinical efficacy beyond the multiple clinical trials completed or underway using CDCs or the CDC secretome.

Conflict of interest: none declared.

References are available as supplementary material at European Heart Journal online.

Published by Oxford University Press on behalf of the European Society of Cardiology 2019.

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Snow and ice cause cars to stall out on the road to their destination. In patients with CLL, its their stem cells that stall out and researchers want to know why.

For patients who have chronic lymphocytic leukemia, fighting off a serious infection can be difficult and often is just not possible. And a team of Mayo researchers is starting to find out why in a paper published recently in the journal Leukemia.

What is Chronic Lymphocytic Leukemia?

This disease is cancer of an immune cell called a B lymphocyte. These cells form in bone marrow and migrate out to patrol in the blood stream and lymphoid organs. But in chronic lymphocytic leukemia, the immune system is depleted, a state called immunodeficiency. Because of that, people with this type of leukemia are prone to serious infections and the diseases those may cause. They are also prone to developing other types of cancer.

And its those resulting problems that may ultimately contribute to death explains Kay Medina, Ph.D., a Mayo Clinic immunologist. Dr. Medina specializes in how immune cells develop from bone marrow stem cells.

In our bone marrow, stem cells convert to red blood cells, platelets or a variety of immune cells. Those are then sent into the blood stream where they do their job. Red blood cells replace cells that are worn out.

White blood cells patrol the byways of our circulation, chasing down everything from cellular debris to bacteria to virus particles.But not in patients with chronic lymphocytic leukemia.

Joining the Team

Research on chronic lymphocytic leukemia is going on in several labs at Mayo Clinic. Dr. Medina got involved after speaking with colleagues Wei Ding, M.B.B.S, Ph.D., and Neil Kay, M.D., both chronic lymphocytic leukemia physician researchers.

Mayo has a strong tradition of encouraging physician/basic research collaborations to advance knowledge of disease mechanisms, development, and assessment of new treatment approaches, says Dr. Medina.

The basic research helps us understand the cause of the disease, in this case the leukemia cell, but it also helps to understand what the disease does to other parts of the body, such as the lymph nodes, spleen, blood and bone marrow, she says.

Bone marrow is the organ that replenishes all cells in the immune system but has not been evaluated for functional proficiency in CLL patients, explains Dr. Medina.

Checking out the Cells and their Environment

Kay Medina, Ph.D.

Dr. Medinas team, with funding from Mayo Clinics Center for Biomedical Discovery, decided to look at bone marrow stem cells and their ability to generate all blood cell types. Some of the immune deficiency may be the result of treatment, but untreated patients have the same problem. The chronic nature of the disease itself may also dampen immune activity. But Dr. Medina explains that the leukemia cells may promote an environment that suppresses immune function.

Our research seeks to add to the discussion by identifying additional ways patients with CLL are unable to fight off tumors and other diseases, says Dr. Medina.

In a paper published late last year, Dr. Medina and her team, including first author Bryce Manso who is a student in the Mayo Clinic Graduate School of Biomedical Sciences, examined bone marrow and blood samples from chronic lymphocytic leukemia patients and healthy controls to determine the frequency of bone marrow stem cells in each sample and how well they did their job.

Bryce Manso, presenting a poster to a conference attendee.

The authors reported that, in general, samples from patients with chronic lymphocytic leukemia have fewer stem cells in their bone marrow, and those stem cells that remain work less well than stem cells from controls.

Stalled-Out Bone Marrow Stem Cells

As to why this happens, the authors found that it was linked to loosening controls for the on/off switches which regulate this process, proteins called transcription factors. These proteins regulate key functions in the cell, and are out of whack in samples from chronic lymphocytic leukemia patients. They may prevent bone marrow stem cells from pursuing a pathway for development; stalling-out their ability to differentiate, resulting in decreased production of important blood cells that provide the first line of defense against infectious agents.

But, Dr. Medina cautions, there is more to this story.

This is an emerging area of research in that its both a unique explanation for the clinical problem of immune deficiency and it has been minimally studied, says Dr. Medina. Future studies are planned to look at specific transcription factors that control stem cell differentiation as well as how the presence of leukemic cells in the bone marrow alter blood cell development. They will then relate this information to clinically relevant complications reported in chronic lymphocytic leukemia patients, she says.

Basic Research to Improve Patient Care

Dr. Medina, her team, and their clinical colleagues hope that by understanding how bone marrow function is impaired in chronic lymphocytic leukemia patients, they can develop unique strategies to boost bone marrow function or find alternate treatments that do not block or modify marrow function.

Through this work we hope to find ways to reduce infections and the incidence of second cancers in chronic lymphocytic leukemia patients. Our research has the potential to improve quality of life as well as extend the lives of these patients says Dr. Medina.

###

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Tags: basic science, blood cancer, cancer, Center for Biomedical Discovery, chronic lymphocytic leukemia, Findings, immunology, Kay Medina, leukemia, Mayo Clinic Cancer Center, Neil Kay, News, Progress Updates, Wei Ding

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Stem cell therapies have come a long way since the 1970s and 1980s. Today the ethical issues of harvesting stem cells have long been resolved through the discovery of several sources of potent stem cell types. Common sources include in the umbilical cord and placenta (post birth), bone marrow, and the fatty layer that lies just beneath everyones skin (adipose fat tissue). Of these resources, by far the most commonly accessed in the United States are adipose fat and bone marrow stem cells.The National Stem Cell Institute (NSI), a leading stem cell clinic in the U.S., has seen the development of these living resources usher in an exciting new age known as regenerative medicine. Because of their potency and new technologies that allow ease of access, stem cells are changing the very face of medicine. In particular, the harvesting of bone marrow stem cells has developed into a procedure that is minimally invasive, far more comfortable than bone marrow harvesting of the past, and able to be complete in just a few hours.Some Basics About Bone Marrow Stem CellsBone marrow is the living tissue found in the center of our bones. Marrow is a soft, sponge-like tissue. There are two types of bone marrow: red marrow and yellow marrow. In adults, red marrow is found mainly in the central skeleton, such as the pelvis, sternum, cranium, ribs, vertebrae, and scapulae. But it is also found in the ends of long bones such as in the arms and legs.When it comes to bone marrow stem cells, red marrow is what its all about. Red marrow holds an abundance of them. Stem cells are a kind of protocell that has not yet been assigned an exact physical or neurological function. You can think of them as microscopic packets of potential that stay on high alert for signals telling them where they are needed and what type of cell they need to become.Bone marrow stem cells are multipotent, which means they have the ability to become virtually any type of tissue cell, including:

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As the body ages, its only natural that some of its processes should break down. Humans become clumsier, stiffer, their reaction times slower, their senses duller. This is often due to the fact that nerves in the extremities grow less sensitive over time, transmitting messages to the brain more slowly and feeling less acutely a condition known as peripheral neuropathy or simply neuropathy.

While some of that is normal, especially in the golden years, neuropathy often manifests in people much too young in their 30s, 40s, or 50s as a result of a disease such as diabetes or autoimmune issues. Unfortunately, the condition can significantly hamper a persons quality of life, making mobility difficult and limiting everyday activities.

The good news? Neuropathy may have a cure, or at least a solid treatment, on the horizon. Stem cells show great promise for a wide variety of conditions, and nerve damage is the latest of these. To see how it can help, its important to understand what stem cell treatment is, what neuropathy is and what causes it, and how the former can address the latter.

In this article:

The body is made of trillions of tissue-specific cells, making up organs, skin, muscle, bone, nerves, and all other tissue. Some of these can renew indefinitely, such as blood cells. Others, however, cannot replace themselves: Once they have divided a certain number of times or become damaged, theyre dead for good. That goes for nerves and brain tissue, for example.

There is, however, an answer. The developing embryo uses stem cells, or master cells capable of differentiating into any kind of tissue in the human body, to transform one fertilized egg into a fully functional baby human. While adult humans lack these pluripotent stem cells that can transform into anything, they do have multipotent stem cells, which are tissue-specific master cells (such as blood cells).

By harvesting these multipotent stem cells from blood or fat tissue, scientists can induce the cells to become pluripotent, meaning theyre now capable of becomingany tissue in the human body. Essentially, researchers have figured out how to reverse-engineer adult stem cells to become all-powerful embryonic cells. This meansstem cells have a huge range of possible uses.

In other cases, multipotent stem cells alone are enough to heal some parts of the human bodysuch as nerves.

Peripheral neuropathymanifests in a number of ways. It causes pain, weakness, and tingling in affected areas, making it hard to lift objects, grasp items, walk competently, and more. Typically it affects the hands and feet most strongly, though it can also cause symptoms in the arms, legs, and face. Not only does it affect motor coordination,but it also makes it hard for the body to sense the environment, including temperature, pain, vibration, and touch.

A more serious manifestation of the disease is autonomic neuropathy, which influences more than the periphery of the body. It also messes with blood pressure, bladder and bowel function, digestion, sweating, and heart rate. Polyneuropathy is when the condition starts at the periphery of the body but gradually spreads inward.

Diabetic neuropathy is the most well-known incarnation of this disease. It is a result of high glucose and fat levels in the blood, which can damage nerves.Other causes include:

If the bad news is there are so many potential causes of neuropathy, the good news is stem cell treatments have the potential to address all of them.

In the case of neuropathy, stem cell treatment is simpler than in other conditions. Mesenchymal stem cells (certain types of multipotent stem cells) releaseneuroprotective and neuroregenerative factors, so when they are injected into the bloodstream they can begin to rebuild nerves and undo the damage caused by the disease. Also, because these stem cells replicate indefinitely, they will offer these benefits for the rest of the patients life.

The basic process is that scientists harvest these cells from the patient (autologous transplant) or from a donor (allogeneic transplant), then cultivate them until they reach certain levels before reinjecting them back into the patient. The stem cells, with the help of hormones and growth factors, seek out and repair the damage done by neuropathy.

The main risks to stem cell treatment include reaction to the injection. In an autologous transplant, the patient may react to the preservatives and other chemicals used by way of necessity. In an allogeneic transplant, the patient may exhibit an immune response to donor cells, or vice versa with the donor cells seeing the patients body as an invader and attacking it. All of the above reactions can prove minor or, on the other end of the spectrum, fatal.

The severity of the problem will, therefore, dictate whether or not it is worth moving forward. Note that those whodochoose to pursue the treatment often have extremely good results.

Unlike some other stem cell treatments, which remain in preliminary stages, stem cell therapy for neuropathy has thus far received serious attention. However, thesmall sample size and difficult conditions of clinical trialsmake it hard to say yet whether this treatment will become widespread or receive FDA approval.Other studies have demonstrated more significant resultsin the treatment of facial pain and may pave the way for future neuropathy treatments using stem cells.

For now, those suffering from neuropathy should seek the advice of a physician. If there are clinical trials available nearby, thats the place to start. Its possible to seek stem cell therapy through a clinic as well as through a clinical study or research institution, but make sure to research the provider thoroughly. With stem cells becoming such a relevantapproach to medical conditions of all kinds, its not safe to conclude that all providers are equally experienced or effective.

If you found this blog valuable, subscribe to BioInformants stem cell industry updates.

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Did this article address your concerns about neuropathy? Let us know in the comments section below.

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Stem Cell Therapy for Neuropathy: What Can We Expect

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Overview

If you are planning to donate stem cells, you have agreed to allow doctors to draw bone marrow stem cells from either your blood or bone marrow for transplantation.

There are two broad types of stem cells: embryonic and bone marrow stem cells. Embryonic stem cells are studied in therapeutic cloning and other types of research. Bone marrow stem cells are formed and mature in the bone marrow and are then released into the bloodstream. This type of stem cell is used in the treatment of cancers.

In the past, surgery to draw bone marrow stem cells directly from the bone was the only way to collect stem cells. Today, however, it's more common to collect stem cells from the blood. This is called peripheral blood stem cell donation.

Stem cells can also be collected from umbilical cord blood at birth. However, only a small amount of blood can be retrieved from the umbilical cord, so this type of transplant is generally reserved for children and small adults.

Every year, thousands of people in the U.S. are diagnosed with life-threatening diseases, such as leukemia or lymphoma, for which a stem cell transplant is the best or the only treatment. Donated blood stem cells are needed for these transplants.

You might be considering donating blood or bone marrow because someone in your family needs a stem cell transplant and doctors think you might be a match for that person. Or perhaps you want to help someone else maybe even someone you don't know who's waiting for a stem cell transplant.

Bone marrow stem cells are collected from the posterior section of the pelvic bone under general anesthesia. The most serious risk associated with donating bone marrow involves the use and effects of anesthesia during surgery. After the surgery, you might feel tired or weak and have trouble walking for a few days. The area where the bone marrow was taken out might feel sore for a few days. You can take a pain reliever for the discomfort. You'll likely be able to get back to your normal routine within a couple of days, but it may take a couple of weeks before you feel fully recovered.

The risks of this type of stem cell donation are minimal. Before the donation, you'll get injections of a medicine that increases the number of stem cells in your blood. This medicine can cause side effects, such as bone pain, muscle aches, headache, fatigue, nausea and vomiting. These usually disappear within a couple of days after you stop the injections. You can take a pain reliever for the discomfort. If that doesn't help, your doctor can prescribe another pain medicine for you.

For the donation, you'll have a thin, plastic tube (catheter) placed in a vein in your arm. If the veins in your arms are too small or have thin walls, you may need to have a catheter put in a larger vein in your neck, chest or groin. This rarely causes side effects, but complications that can occur include air trapped between your lungs and your chest wall (pneumothorax), bleeding, and infection. During the donation, you might feel lightheaded or have chills, numbness or tingling around your mouth, and cramping in your hands. These will go away after the donation.

If you want to donate stem cells, you can talk to your doctor or contact the National Marrow Donor Program, a federally funded nonprofit organization that keeps a database of volunteers who are willing to donate.

If you decide to donate, the process and possible risks of donating will be explained to you. You will then be asked to sign a consent form. You can choose to sign or not. You won't be pressured to sign the form.

After you agree to be a donor, you'll have a test called human leukocyte antigen (HLA) typing. HLAs are proteins found in most cells in your body. This test helps match donors and recipients. A close match increases the chances that the transplant will be a success.

If you sign up with a donor registry, you may or may not be matched with someone who needs a blood stem cell transplant. However, if HLA typing shows that you're a match, you'll undergo additional tests to make sure you don't have any genetic or infectious diseases that can be passed to the transplant recipient. Your doctor will also ask about your health and your family history to make sure that donation will be safe for you.

A donor registry representative may ask you to make a financial contribution to cover the cost of screening and adding you to the registry, but this is usually voluntary. Because cells from younger donors have the best chance of success when transplanted, anyone between the ages of 18 and 44 can join the registry for free. People ages 45 to 60 are asked to pay a fee to join; age 60 is the upper limit for donors.

If you're identified as a match for someone who needs a transplant, the costs related to collecting stem cells for donation will be paid by that person or by his or her health insurance.

Collecting stem cells from bone marrow is a type of surgery and is done in the operating room. You'll be given an anesthetic for the procedure. Needles will be inserted through the skin and into the bone to draw the marrow out of the bone. This process usually takes one to two hours.

After the bone marrow is collected, you'll be taken to the recovery room while the anesthetic wears off. You may then be taken to a hospital room where the nursing staff can monitor you. When you're fully alert and able to eat and drink, you'll likely be released from the hospital.

If blood stem cells are going to be collected directly from your blood, you'll be given injections of a medication to stimulate the production of blood stem cells so that more of them are circulating in your bloodstream. The medication is usually started several days before you're going to donate.

During the donation, blood is usually taken out through a catheter in a vein in your arm. The blood is sent through a machine that takes out the stem cells. The rest of the blood is then returned to you through a vein in your other arm. This process is called apheresis. It takes two to six hours and is done as an outpatient procedure. You'll typically undergo two to four apheresis sessions, depending on how many blood stem cells are needed.

Recovery times vary depending on the individual and type of donation. But most blood stem cell donors are able to return to their usual activities within a few days to a week after donation.

Recovery times vary depending on the individual and type of donation. But most blood stem cell donors are able to return to their usual activities within a few days to a week after donation.

Explore Mayo Clinic studies testing new treatments, interventions and tests as a means to prevent, detect, treat or manage this disease.

Dec. 20, 2018

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Blood and bone marrow stem cell donation - Mayo Clinic

Bone Marrow Stem Cells Comments Off on Blood and bone marrow stem cell donation – Mayo Clinic | March 24th, 2019

Bone Marrow (BM) contains hematopoietic stem/progenitor cells, which have the potential to self-renew, proliferate, and differentiate into multi-lineage blood cells. Multipotent, non-hematopoietic stem cells, such as mesenchymal stem cells, can be isolated from human BM as well. These non-hematopoietic, mesenchymal stem cells are capable of both self-renewal and differentiation into bone, cartilage, muscle, tendons, and fat. BM is drawn into a 60cc syringe containing heparin (80 U/mL of BM) from the posterior iliac crest, 25 mL/site, from a maximum of four sites.CustomizationLet us know how we can customize your product today Custom InquiryDonor CriteriaAge18-65 years oldWeight>= 130 lbsScreened before donationHIV (HIV 1 & 2 Ab)HBV (Surface Antigen HbsAg)HCV (HCVAb)Donation FrequencyMinimum 10 weeks between donationsDonors with any of the following will be excluded from donatingPregnancyHistory of heart, lung, liver, or kidney diseaseHistory of asthmaBlood and bleeding disorders including sickle cell diseaseNeurologic disordersAutoimmune disordersCancerDiabetesOther CriteriaMust be in general good healthMust have accessible hipsComplete Blood Count lab test must meet protocol specsRequired to sign procedure-specific consent form

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Whole Bone Marrow - AllCells.com

Bone Marrow Stem Cells Comments Off on Whole Bone Marrow – AllCells.com | March 23rd, 2019

CAR-T cell therapy is asa type of immunotherapy that teaches T cells to recognize and destroy cancer.CAR-T cell therapy has demonstrated promising results in a range of patients from young and old. In some patients, this can lead to the total elimination of the cancer. In others, there is a significant improvement of the disease.

For those who are facing cancer, it is important to answer the question What is CAR-T? This guide will answer the most common questions about CAR-T cell therapy for readers who want to understand this novel technology platform for treating cancer.

What you need to know about CAR-T therapy and its role in cancer treatment is described below.

CAR-T is pronounced phonetically, as car tee cell.CAR-T is named after a mythical creature called the chimera. A chimera is an animal made of different parts of different animals attached together.

With CAR-T cell therapy, apatientsTcells are modified within a laboratory, so that they they can find and attack cancer cells. Because CAR-T cells combine different parts from different sources, they are called chimera (meaning, blended or fused) antigen receptor T cells.

T cells are a type of white bloodcell that plays a central role in the immune response within humans.T cell that have been genetically altered into CAR-T cells function as living drugs when they are administered to patients.

To understand CAR-T cell therapy,a brief history of immunologymay prove helpful. An antigen is a foreign substance in the body, either a toxin or disease agent or unhealthy cell (as in cancer), that triggers an immune response. The body then produces white blood cells to attack the agent. It does this by binding to it with the use of antigen receptors on the surface of the white blood cells, or lymphocytes. Only then does the body produce antibodies to destroy the foreign or diseased agent.

The problem is T cells, the white blood cells responsible for destroying tumor cells,are not good enough at recognizing it. Therefore, in order to increase the patient immune levels, medical specialists take blood. From the blood, they harvest T cells and add extra antigen receptors to the surface of the cells. They inject those cells back into the patient via blood transfusion, where they multiply and can then attack cancer, either with or without the aid of additional therapies.

Specifically, the antigens can then recognize the protein CD-19, which forms on the surface of B cells, a type of blood cell that frequently becomes cancerous. By knowing which proteins to look for, the modified T cells can hunt them down, attack, and destroy them throughout the bloodstream.

CAR-T cells are defined as T-cells (immune cells) that have been modified to match markers present on the outside of cancer cells, allowing them to selectively find and attack them. To create CAR-T cells, physicians extract T-cells from a patient, genetically alter them, expand them in quantity, and re-infuse them to the patient so that the engineered CAR-T cell can selectively attack cancer cells.

The patient response is then monitored using a variety of tools.

There are four steps involved with the CAR-T cell therapy process.

These steps include:

The patient is then monitored by the attending physicians to document the therapeutic response.

Cancer is a silent killer. Too often, it has devastating results, because the cells in the human body are not adept at killingit. This is the case with T cells, human immune cells whose responsibility is to fight invasion and disease. These cells, also known as T lymphocytes a special type of white blood cell are not always able to recognize and eliminate cancer.A potential new solution may be CAR-T cell therapy.

As theCancer Treatment Centers of Americapoints to CAR-T treatment as a novel way to treat cancer, it could drastically alter the medical outlook for both children and adults. These patients would otherwise be without the possibility of a cure.

However, CAR-T immunotherapy is not a cure-all for every patient. For some, it only works for a short time before the cancer relapses. Other patients respond to it, but suffer such severe side effects that it does almost nothing to ease the symptoms. While researchers work furiously to determine why some treatments work on cancer cells and others do not, they still have not arrived at a firm answer.

During transport and until ready to administer at bedside CAR-T cells must be stored at least -150 Celsius. @SylvesterCancer is the only center in South Florida certified to treat patients with this novel #immunotherapy pic.twitter.com/1LKm6UHzd8

Sylvester Cancer (@SylvesterCancer) August 7, 2018

In 2017, two experimental CAR-T treatments received approval from the U.S. FDA with more in clinical trials:

Kymriah was approved by FDA in August 2017 to be used in children and adults with ALL. In May 2018, the FDA approved Kymriah for a second indication (diffuse large B-cell lymphoma). The second CAR-T product, Yescarta, was approved by FDA in October 2017 for patients with lymphoma.In August 2018, both Kymriah and Yescarta secured European regulatory approval. In September 2018, Health Canada made Kymriah the first CAR-T therapy to receive regulatory approval in Canada.

Numerous companies are also working to perfect the technology of CAR-T cells. Akron Biotechmodifies many types of cells for use in medical treatments.

CAR-T is a new technology. Not only is it expensive to manufacture antigens in a lab and attach them to T cells, it takes a long time and carries a number of different specifications in order for candidates to gain approval for the treatment. So, exactly which candidates can receive therapy?

Both treatment protocols modify T cells to help them recognize and attack diseased B cells in the blood. Patients with either leukemia or B-cell lymphoma may apply for the clinical trial at this time. However, they cannot do so without first trying at least two other cancer therapies of a more standard nature.

Currently, researchers are experimenting with CAR-T therapies for other types of cancers as well. These include leukemia and lymphoma subtypes, as well as non-blood-borne cancers. Its ability to fight solid tumors, or those that do not spread throughout blood or bone marrow, have thus far proven less than impressive.

Physicians make CAR-T cells via a careful process. First, the patient is set up in the hospital and prepped for a blood draw, followed by a long stay. Most patients are quite ill by the time they start CAR-T cell immunotherapy, necessitating they remain in the hospital until the completion of the treatment.

Doctors then take a patients blood and feed it into anapheresis machine. This device separates out the white blood cells, T cells included. Then it feeds the remaining blood back to the patient. This means they do not lose a lot of blood while physicians now have a healthy supply of cells to transform. Doctors then freeze the harvested cells and send them off to a lab.

Lab workers then take the collected T cells and introduce a gene that manufactures the chimeric antigen receptor into the DNA of each cell. Lab workers then grow millions of versions of these cells. Once they have enough, they harvest the cells, freeze them once more and deliver them back to the patient via transfusion.

Both these T cells, plus the ones subsequently manufactured by the patients body, can then bind to and attack the cancer cells.

Because transforming T cells is such a complex process, the treatment is typically a long one for the patient. From beginning to end, the transformation and reintroduction of cells may take up to 3 weeks. During that time, the patient is compromised even more than usual due to the reduction in their T cell population. Thats why they usually stay in the hospital during the entire process. This way, doctors can monitor them and make sure their immunity stays as robust as possible.

Before introducing the modified T cells to the patient, physicians typically give them a round of chemotherapy. This helps to weaken their immune system further, which reduces the chances that existing T cells will outnumber the new ones. Counterintuitively, by depressing the immune system in the short run, doctors give patients the best chance of engineered T cells multiplying and doing their job.

The transfusion itself is typically short and painless, lasting only about an hour. After staying in the hospital for monitoring, patients must come in regularly for a few weeks afterward.

The huge benefit of a treatment like this is the T cell modifications will last for life. Each time a bodys T cells encounter a toxin or disease agent and develop antigen receptors and antibodies to fight it, the person has that ability forever. That means patients who receive modified T cells now have the tools to fight their particular cancer for the remainder of their days.

This makes CAR-T cell therapy more than a treatment. For example, while chemotherapy and radiation are effective, their curative effects end when the treatment ends (or, more accurately, a few days or weeks after the last course). In contrast, modified T cells hang aroundforever, turning this type of immunotherapy into a living drug.

While CAR-T therapies are long-lasting, making them more affordable over a lifetime, it is expensive to access these therapies.Currently, Kymriah and Yescarta are offered at the following prices:

Moreover, possible side effects do exist. These include:

Finally, while the process is very beneficial to some patients, it is extremely time-consuming. Some question where it can actually serve the broader population, considering the necessary time and specialization required.

Do you need a visual look at how CAR-T therapy works? Watch this video from Associated Press.

CAR-T companies are on the rise, supported by growing investment flowing into CAR-T product development and landmark approvals of CAR-T cell therapies by the U.S. FDA, European Medicines Agency (EMA), and Health Canada.

Are you interested to know the identities of the companies developing CAR-T therapies worldwide?

For a limited-time, you can claim the Global Database of CAR-T Cell Therapy Companies and get the CAR-T Funding Brief ($49 value) for FREE:

Overall, T-cell therapy has proven a promising new treatment approach. As its manufacture, administration, and safety profile improve, it will become an important tool in the cancer treatment toolkit.

Do you know anyone in need of a cancer cure? What role could CAR-T therapy play in their treatment? Let us know in the comments below.

What is CAR-T Cell Therapy? | CAR-T Definition

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What is CAR-T Cell Therapy | CAR-T Definition | Bioinformant

IPS Cell Therapy Comments Off on What is CAR-T Cell Therapy | CAR-T Definition | Bioinformant | March 17th, 2019

Together, the brain and spinal cord form the central nervous system. This complex system is part of everything we do. It controls the things we choose to do -- like walk and talk -- and the things our body does automatically -- like breathe and digest food. The central nervous system is also involved with our senses -- seeing, hearing, touching, tasting, and smelling -- as well as our emotions, thoughts, and memory.

The brain is a soft, spongy mass of nerve cells and supportive tissue. It has three major parts: the cerebrum, the cerebellum, and the brain stem. The parts work together, but each has special functions.

The cerebrum, the largest part of the brain, fills most of the upper skull. It has two halves called the left and right cerebral hemispheres. The cerebrum uses information from our senses to tell us what's going on around us and tells our body how to respond. The right hemisphere controls the muscles on the left side of the body, and the left hemisphere controls the muscles on the right side of the body. This part of the brain also controls speech and emotions as well as reading, thinking, and learning.

The cerebellum, under the cerebrum at the back of the brain, controls balance and complex actions like walking and talking.

The brain stem connects the brain with the spinal cord. It controls hunger and thirst and some of the most basic body functions, such as body temperature, blood pressure, and breathing.

The brain is protected by the bones of the skull and by a covering of three thin membranes called meninges. The brain is also cushioned and protected by cerebrospinal fluid. This watery fluid is produced by special cells in the four hollow spaces in the brain, called ventricles. It flows through the ventricles and in spaces between the meninges. Cerebrospinal fluid also brings nutrients from the blood to the brain and removes waste products from the brain.

The spinal cord is made up of bundles of nerve fibers. It runs down from the brain through a canal in the center of the bones of the spine. These bones protect the spinal cord. Like the brain, the spinal cord is covered by the meninges and cushioned by cerebrospinal fluid.

Spinal nerves connect the brain with the nerves in most parts of the body. Other nerves go directly from the brain to the eyes, ears, and other parts of the head. This network of nerves carries messages back and forth between the brain and the rest of the body

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About The Brain and Spinal Cord | Neurosurgery ...

Spinal Cord Stem Cells Comments Off on About The Brain and Spinal Cord | Neurosurgery … | March 16th, 2019

Before the transplant admission:

When the healthcare team decides that BMT is the best treatment option for your child, they will schedule a lengthy conversation with you to explain the procedure. They will explain the many risks associated with BMT, as well as what you can expect before, during, and after the transplant.

Your child will undergo testing to make sure he/she is healthy enough to withstand the rigors of transplant. Testing will include evaluation of the heart function with electrocardiogram (ECG) and kidney and liver function, and infection status. Depending upon the disease, a bone marrow aspirate and spinal tap may be performed.

When your child is deemed healthy enough for BMT, physicians will usually insert a central line catheter that allows easy access to a large vein in the chest. The catheter will be used to deliver the new stem cells, as well as blood, antibiotics, and other medications during treatment.

Preparation Before Transplant:

Your child will be given preparative treatment, called conditioning before the transplant. Conditioning includes high doses of chemotherapy and sometimes, radiation of the whole body. The type and purpose of conditioning depends upon your childs underlying diagnosis but may include:

Commonly used drugs include:

The Transplant

Once conditioning is complete, stem cells are given through a catheter. This is very similar to a blood transfusion. After traveling through the bloodstream to the bone marrow, the transplanted stem cells will begin to make red and white blood cells, and platelets.

It can take between 14 and 30 days for enough blood cells, particularly white blood cells, to be created so the body can fight infection. The identification of new blood cells and an increase in white blood cells following BMT is called engraftment. Until then, your child will be at a high risk for infection, anemia, and bleeding. Your child will remain in the hospital until he or she is well enough for discharge.

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Bone Marrow Transplant | CureSearch

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Definition

A bone marrow transplant is a procedure to replace damaged or destroyed bone marrow with healthy bone marrow stem cells.

Bone marrow is the soft, fatty tissue inside your bones. The bone marrow produces blood cells. Stem cells are immature cells in the bone marrow that give rise to all of your different blood cells.

Transplant - bone marrow; Stem cell transplant; Hematopoietic stem cell transplant; Reduced intensity nonmyeloablative transplant; Mini transplant; Allogenic bone marrow transplant; Autologous bone marrow transplant; Umbilical cord blood transplant; Aplastic anemia - bone marrow transplant; Leukemia - bone marrow transplant; Lymphoma - bone marrow transplant; Multiple myeloma - bone marrow transplant

Before the transplant, chemotherapy, radiation, or both may be given. This may be done in 2 ways:

There are three kinds of bone marrow transplants:

A stem cell transplant is usually done after chemotherapy and radiation is complete. The stem cells are delivered into your bloodstream usually through a tube called a central venous catheter. The process is similar to getting a blood transfusion. The stem cells travel through the blood into the bone marrow. Most times, no surgery is needed.

Donor stem cells can be collected in two ways:

A bone marrow transplant replaces bone marrow that is either not working properly or has been destroyed (ablated) by chemotherapy or radiation. Doctors believe that for many cancers, the donor's white blood cells may attack any remaining cancer cells, similar to when white cells attack bacteria or viruses when fighting an infection.

Your health care provider may recommend a bone marrow transplant if you have:

A bone marrow transplant may cause the following symptoms:

Possible complications of a bone marrow transplant depend on many things, including:

Complications may include:

Your provider will ask about your medical history and do a physical exam. You will have many tests before treatment begins.

Before transplant, you will have 1 or 2 tubes, called catheters, inserted into a blood vessel in your neck or arms. This tube allows you to receive treatments, fluids, and sometimes nutrition. It is also used to draw blood.

Your provider will likely discuss the emotional stress of having a bone marrow transplant. You may want to meet with a counselor. It is important to talk to your family and children to help them understand what to expect.

You will need to make plans to help you prepare for the procedure and handle tasks after your transplant:

A bone marrow transplant is usually done in a hospital or medical center that specializes in such treatment. Most of the time, you stay in a special bone marrow transplant unit in the center. This is to limit your chance of getting an infection.

Depending on the treatment and where it is done, all or part of an autologous or allogeneic transplant may be done as an outpatient. This means you do not have to stay in the hospital overnight.

How long you stay in the hospital depends on:

While you are in the hospital:

After you leave the hospital, be sure to follow instructions on how to care for yourself at home.

How well you do after the transplant depends on:

A bone marrow transplant may completely or partially cure your illness. If the transplant is a success, you can go back to most of your normal activities as soon as you feel well enough. Usually it takes up to 1 year to recover fully, depending on what complications occur.

Complications or failure of the bone marrow transplant can lead to death.

Bashir Q, Champlin R. Hematopoietic stem cell transplantation. In: Niederhuber JE, Armitage JO, Doroshow JH, Kastan MB, Tepper JE, eds. Abeloff's Clinical Oncology. 5th ed. Philadelphia, PA: Elsevier Saunders; 2014:chap 30.

Heslop HE. Overview and choice of donor of hematopoietic stem cell transplantation. In: Hoffman R, Benz EJ, Silberstein LE, et al, eds. Hematology: Basic Principles and Practice. 7th ed. Philadelphia, PA: Elsevier; 2018:chap 103.

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Bone marrow transplant | UF Health, University of Florida ...

Bone Marrow Stem Cells Comments Off on Bone marrow transplant | UF Health, University of Florida … | March 13th, 2019