Category Archives: Stem Cells

One of the current challenges for stem cell researchers is to understand how all the skin appendages are regenerated. This could lead to improved treatments for burn patients, or others with severe skin damage.

Researchers are also working to identify new ways to grow skin cells in the lab. Epidermal stem cells are currently cultivated on a layer of cells from rodents, called feeder cells. These cell culture conditions have been proved safe, but it would be preferable to avoid using animal products when cultivating cells that will be transplanted into patients. So, researchers are searching for effective cell culture conditions that will not require the use of rodent cells.

Scientists are also working to treat genetic diseases affecting the skin. Since skin stem cells can be cultivated in laboratories, researchers can genetically modify the cells, for example by inserting a missing gene. The correctly modified cells can be selected, grown and multiplied in the lab, then transplanted back onto the patient. Epidermolysis Bullosa is one example of a genetic skin disease, where patients can benefit from this approach. Work is underway to test the technique.

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Skin stem cells: where do they live and what can they do ...

The onlinevideoseems to promise everything an arthritis patient could want.

The six-minute segment mimics a morning talk show, using a polished TV host to interview guests around a coffee table. Dr. Adam Pourcho extols the benefits of stem cells and regenerative medicine for healing joints without surgery. Pourcho, a sports medicine specialist, says he has used platelet injections to treat his own knee pain, as well as a tendon injury in his elbow. Extending his arm, he says, Its completely healed.

Brendan Hyland, a gym teacher and track coach, describes withstanding intense heel pain for 18 months before seeing Pourcho. Four months after the injections, he says, he was pain-free and has since gone on a 40-mile hike.

I dont have any pain that stops me from doing anything I want, Hyland says.

Critics suggest the hospitals are exploiting desperate patients and profiting from trendy but unproven treatments.

The videos cheerleading tone mimics theinfomercialsused to promote stem cell clinics, several of which have recently gotten into hot water with federal regulators, saidDr. Paul Knoepfler, a professor of cell biology and human anatomy at the University of California-Davis School of Medicine. But the marketing video wasnt filmed by a little-known operator.

It was sponsored bySwedishMedical Center, the largest nonprofit health provider in the Seattle area.

Swedish is one of a growing number ofrespected hospitalsandhealth systems including theMayo Clinic, theCleveland Clinicand theUniversity of Miami that have entered the lucrative business ofstem cellsandrelated therapies, including platelet injections. Typical treatments involveinjecting patients joints with their own fatorbone marrowcells, or with extracts ofplatelets, the cell fragments known for their role in clotting blood. Many patients seek out regenerative medicine to stave off surgery, even though theevidencesupporting these experimental therapies isthin at best, Knoepfler said.

Hospitals say theyre providing options to patients who have exhausted standard treatments. But critics suggest the hospitals are exploiting desperate patients and profiting from trendybut unproventreatments.

TheFood and Drug Administrationis attempting to shut down clinics that hawk unapproved stem cell therapies, which have been linked toseveral cases of blindnessand atleast 12 serious infections. Although doctors usually need preapproval to treat patients with human cells, the FDA has carved out ahandful of exceptions,as long as the cells meet certain criteria, said Barbara Binzak Blumenfeld, an attorney who specializes in food and drug law at Buchanan Ingersoll & Rooney in Washington.

Hospitals like Mayo are careful to follow these criteria, to avoid running afoul of the FDA, said Dr. Shane Shapiro, program director for the Regenerative Medicine Therapeutics Suites at Mayo Clinics campus in Florida.

While hospital-based stem cell treatments may be legal, theres nostrong evidencethey work, said Leigh Turner, an associate professor at the University of Minnesotas Center for Bioethics who has published a series of articles describing the size and dynamics of thestem cell market.

FDA approval isnt needed and physicians can claim they arent violating federal regulations, Turner said. But just because something is legal doesnt make it ethical.

For doctors and hospitals, stem cells are easy money, Turner said. Patients typically paymore than $700a treatment for platelets and up to$5,000for fat and bone marrow injections. As a bonus, doctors dont have to wrangle with insurance companies, which view the procedures asexperimentaland largelydont cover them.

For doctors and hospitals, stem cells are easy money.

Its an out-of-pocket, cash-on-the-barrel economy, Turner said. Across the country, clinicians at elite medical facilities are lining their pockets by providingexpensive placebos.

Some patient advocates worry that hospitals are more interested in capturing a slice of the stem-cell market than in proving their treatments actually work.

Its lucrative. Its easy to do. All these reputable institutions, they dont want to miss out on the business, said Dr. James Rickert, president of the Society for Patient Centered Orthopedics, which advocates for high-quality care. It preys on peoples desperation.

In a joint statement, Pourcho and Swedish defended the online video.

The terminology was kept simple and with analogies that the lay person would understand, according to the statement. As with any treatment that we provide, we encourage patients to research and consider all potential treatment options before deciding on what is best for them.

But Knoepfler said the guests on the video make several unbelievable claims.

At one point, Dr. Pourcho says thatplatelets release growth factorsthat tell the brain which types of stem cells to send to the site of an injury. According to Pourcho, these instructions make sure that tissues are repaired with the appropriate type of cell, and so you dont get, say, eyeball in your hand.

Knoepfler, who has studied stem cell biology for two decades, said he has never heard of any possibility of growing eyeball or other random tissues in your hand. Knoepfler, who wrote about the video in February on his blog,The Niche, said, Theres no way that the adult brain could send that kind of stem cells anywhere in the body.

The marketing video debuted in July on KING-TV, a Seattle station, as part of a local lifestyles show called New Day Northwest. Although much of the show is produced by the KING 5 news team, some segments like Pourchos interview are sponsored by local advertisers, said Jim Rose, president and general manager of KING 5 Media Group.

After being contacted by KHN, Rose asked Swedish to remove the video from YouTube because it wasnt labeled as sponsored content. Omitting that label could allow the video to be confused with news programming. The video now appears only on the KING-TV website, where Swedish is labeled as the sponsor.

The goal is to clearly inform viewers of paid content so they can distinguish editorial and news content from paid material, Rose said. We value the publics trust.

Federal authorities have recently begun cracking down on doctors who make unproven claims or sell unapproved stem cell products.

In October, theFederal Trade Commissionfined stem cell clinics millions of dollars for deceptive advertising, noting that the companies claimed to be able to treat or cure autism, Parkinsons disease and other serious diseases.

In a recent interview Scott Gottlieb, the FDA commissioner, said the agency will continue to go after what he called bad actors.

Withmore than 700stem cell clinics in operation, the FDA is first targeting those posing the biggest threat, such as doctors who inject stem cells directly into the eye or brain.

There are clearly bad actors who are well over the line and who are creating significant risks for patients, Gottlieb said.

Federal authorities have recently begun cracking down on doctors who make unproven claims or sell unapproved stem cell products.

Gottlieb, set to leave office April 5, said hes also concerned about the financial exploitation of patients in pain.

Theres economic harm here, where products are being promoted that arent providing any proven benefits and where patients are paying out-of-pocket, Gottlieb said.

Dr. Peter Marks, director of the FDAs Center for Biologics Evaluation and Research, said there is a broad spectrum of stem cell providers, ranging from university scientists leading rigorous clinical trials to doctors who promise stem cells are for just about anything. Hospitals operate somewhere in the middle, Marks said.

The good news is that theyre somewhat closer to the most rigorous academics, he said.

The Mayo Clinics regenerative medicine program, for example, focuses conditions such asarthritis, where injections pose few serious risks, even if thats not yet the standard of care, Shapiro said.

Rickert said its easy to see why hospitals are eager to get in the game.

The market for arthritis treatment is huge and growing. At least30 million Americanshave the most common form of arthritis, with diagnoses expected to soar as the population ages. Platelet injections for arthritis generatedmore than $93 millionin revenue in 2015, according to an article last year in The Journal of Knee Surgery.

We have patients in our offices demanding these treatments, Shapiro said. If they dont get them from us, they will get them somewhere else.

Doctors at the Mayo Clinic try to provide stem cell treatments and similar therapies responsibly, Shapiro said. Ina paper published this year,Shapiro described the hospitals consultation service, in which doctors explain patients options and clear up misconceptions about what stem cells and other injections can do. Doctors can refer patients to treatment or clinical trials.

Most of the patients do not get a regenerative [stem cell] procedure, Shapiro said. They dont get it because after we have a frank conversation, they decide, Maybe its not for me.

Although some hospitals boast of high success rates for their stem cell procedures,published researchoften paints a different story.

TheMayo Clinic websitesays that 40 to 70% of patients find some level of pain relief. Atlanta-basedEmory Healthcareclaims that 75 to 80% of patients have had significant pain relief and improved function. In the Swedish video, Pourcho claims we can treat really any tendon or any joint with PRP.

The strongest evidence for PRP is in pain relief for arthritic knees and tennis elbow, where it appears to be safe and perhaps helpful, said Dr. Nicolas Piuzzi, an orthopedic surgeon at the Cleveland Clinic.

But PRP hasnt been proven to help every part of the body, he said.

PRP has been linked to serious complications when injected to treatpatellar tendinitis,an injury to the tendon connecting the kneecap to the shinbone. In a 2013 paper, researchers described the cases of three patients whose pain got dramatically worse after PRP injections. One patient lost bone and underwent surgery to repair the damage.

People will say, If you inject PRP, you will return to sports faster, said Dr. Freddie Fu, chairman of orthopedic surgery at the University of Pittsburgh Medical Center. But that hasnt been proven.

A2017 studyof PRP found it relieved knee pain slightly better than injections of hyaluronic acid. But thats nothing to brag about, Rickert said, given thathyaluronic acid therapy doesnt work, either. While some PRP studies have shown morepositive results, Rickert notes that most were so small orpoorly designedthat theirresults arent reliable.

In its 2013 guidelines for knee arthritis, theAmerican Academy of Orthopaedic Surgeonssaid it is unable to recommend for or against PRP.

PRP is sort of a buyer beware situation, said Dr. William Li, president and CEO of the Angiogenesis Foundation, whose research focuses on blood vessel formation. Its the poor mans approach to biotechnology.

Tests of other stem cell injections also have failed to live up to expectations.

Shapiro published a rigorously designed study last year inCartilage, a medical journal, that found bone marrow injections were no better at relieving knee pain than saltwater injections. Rickert noted that patients who are in pain often get relief from placebos. The more invasive the procedure, the stronger the placebo effect, he said, perhaps because patients become invested in the idea that an intervention will really help. Even saltwater injections help 70% of patients, Fu said.

A 2016 review in theJournal of Bone and JointSurgery concluded that the value and effective use of cell therapy in orthopaedics remain unclear. The following year, a review in theBritish Journal of Sports Medicineconcluded, We do not recommend stem cell therapy for knee arthritis.

Shapiro said hospitals and health plans are right to be cautious.

Many patients have trouble sorting through the hype.

The insurance companies dont pay for fat grafting or bone-marrow aspiration, and rightly so, Shapiro said. Thats because we dont have enough evidence.

Rickert, an orthopedist in Bedford, Ind., said fat, bone marrow and platelet injections should be offered only through clinical trials, which carefully evaluate experimental treatments. Patients shouldnt be charged for these services until theyve been tested and shown to work.

Orthopedists surgeons who specialize in bones and muscles have a history of performing unproven procedures, includingspinal fusion, surgery forrotator cuff diseaseandarthroscopyfor worn-out knees, Turner said. Recently, studies have shown them to be no more effective than placebos.

Some argue that joint injections shouldnt be marketed as stem cell treatments at all.

Piuzzi said he prefers to call the injections orthobiologics,noting that platelets are not even cells, let alone stem cells. The number of stem cells in fat and bone marrow injections is extremely small, he said. In fat tissue, only about 1 in 2,000 cells is a stem cell, according to a March paper inThe Bone & Joint Journal. Stem cells are even rarer in bone marrow, where 1 in 10,000 to 20,000 cells is a stem cell.

Patients are attracted to regenerative medicine because they assume it will regrow their lost cartilage, Piuzzi said. Theres no solid evidence that the commercial injections used today spur tissue growth, Piuzzi said. Although doctors hope that platelets will release anti-inflammatory substances, which could theoretically help calm an inflamed joint, they dont know why some patients who receive platelet injections feel better, but others dont.

So, it comes as no surprise that many patients have trouble sorting through the hype.

Florida resident Kathy Walsh, 61, said she wasted nearly $10,000 on stem cell and platelet injections at a Miami clinic, hoping to avoid knee replacement surgery.

When Walsh heard about a doctor in Miami claiming to regenerate knee cartilage with stem cells, it seemed like an answer to a prayer, said Walsh, of Stuart, Fla. Youre so much in pain and so frustrated that you cling to every bit of hope you can get, even if it does cost you a lot of money.

The injections eased her pain for only a few months. Eventually, she had both knees replaced. She has been nearly pain-free ever since. My only regret, she said, is that I wasted so much time and money.

KaiserHealthNewsis an editorially independent program of the Henry J.KaiserFamily Foundation, a nonprofit, nonpartisanhealthpolicy research and communication organization not affiliated withKaiserPermanente. You can view the original report on itswebsite.

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Why expensive, unproven stem cell treatments are a new ...

Induced pluripotent stem cells (iPSCs) are adult cells that have been genetically reprogrammed to an embryonic stem celllike state by being forced to express genes and factors important for maintaining the defining properties of embryonic stem cells. Although these cells meet the defining criteria for pluripotent stem cells, it is not known if iPSCs and embryonic stem cells differ in clinically significant ways. Mouse iPSCs were first reported in 2006, and human iPSCs were first reported in late 2007. Mouse iPSCs demonstrate important characteristics of pluripotent stem cells, including expressing stem cell markers, forming tumors containing cells from all three germ layers, and being able to contribute to many different tissues when injected into mouse embryos at a very early stage in development. Human iPSCs also express stem cell markers and are capable of generating cells characteristic of all three germ layers.

Although additional research is needed, iPSCs are already useful tools for drug development and modeling of diseases, and scientists hope to use them in transplantation medicine. Viruses are currently used to introduce the reprogramming factors into adult cells, and this process must be carefully controlled and tested before the technique can lead to useful treatment for humans. In animal studies, the virus used to introduce the stem cell factors sometimes causes cancers. Researchers are currently investigating non-viral delivery strategies. In any case, this breakthrough discovery has created a powerful new way to "de-differentiate" cells whose developmental fates had been previously assumed to be determined. In addition, tissues derived from iPSCs will be a nearly identical match to the cell donor and thus probably avoid rejection by the immune system. The iPSC strategy creates pluripotent stem cells that, together with studies of other types of pluripotent stem cells, will help researchers learn how to reprogram cells to repair damaged tissues in the human body.

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Stem Cell Basics VI. | stemcells.nih.gov

Adult stem cells are undifferentiated cells, found throughout the body after development, that multiply by cell division to replenish dying cells and regenerate damaged tissues. Also known as somatic stem cells (from Greek , meaning of the body), they can be found in juvenile as well as adult animals and humans, unlike embryonic stem cells.

Scientific interest in adult stem cells is centered on their ability to divide or self-renew indefinitely, and generate all the cell types of the organ from which they originate, potentially regenerating the entire organ from a few cells.[1] Unlike for embryonic stem cells, the use of human adult stem cells in research and therapy is not considered to be controversial, as they are derived from adult tissue samples rather than human embryos designated for scientific research. They have mainly been studied in humans and model organisms such as mice and rats.

A stem cell possesses two properties:

Hematopoietic stem cells are found in the bone marrow and umbilical cord blood and give rise to all the blood cell types.[3]

Mammary stem cells provide the source of cells for growth of the mammary gland during puberty and gestation and play an important role in carcinogenesis of the breast.[4] Mammary stem cells have been isolated from human and mouse tissue as well as from cell lines derived from the mammary gland. Single such cells can give rise to both the luminal and myoepithelial cell types of the gland, and have been shown to have the ability to regenerate the entire organ in mice.[4]

Intestinal stem cells divide continuously throughout life and use a complex genetic program to produce the cells lining the surface of the small and large intestines.[5] Intestinal stem cells reside near the base of the stem cell niche, called the crypts of Lieberkuhn. Intestinal stem cells are probably the source of most cancers of the small intestine and colon.[6]

Mesenchymal stem cells (MSCs) are of stromal origin and may differentiate into a variety of tissues. MSCs have been isolated from placenta, adipose tissue, lung, bone marrow and blood, Wharton's jelly from the umbilical cord,[7] and teeth (perivascular niche of dental pulp and periodontal ligament).[8] MSCs are attractive for clinical therapy due to their ability to differentiate, provide trophic support, and modulate innate immune response.[7] These cells have the ability to differentiate into various cell types such as osteoblasts, chondroblasts, adipocytes, neuroectodermal cells, and hepatocytes.[9] Bioactive mediators that favor local cell growth are also secreted by MSCs. Anti-inflammatory effects on the local microenvironment, which promote tissue healing, are also observed. The inflammatory response can be modulated by adipose-derived regenerative cells (ADRC) including mesenchymal stem cells and regulatory T-lymphocytes. The mesenchymal stem cells thus alter the outcome of the immune response by changing the cytokine secretion of dendritic and T-cell subsets. This results in a shift from a pro-inflammatory environment to an anti-inflammatory or tolerant cell environment.[10][11]

Endothelial stem cells are one of the three types of multipotent stem cells found in the bone marrow. They are a rare and controversial group with the ability to differentiate into endothelial cells, the cells that line blood vessels.

The existence of stem cells in the adult brain has been postulated following the discovery that the process of neurogenesis, the birth of new neurons, continues into adulthood in rats.[12] The presence of stem cells in the mature primate brain was first reported in 1967.[13] It has since been shown that new neurons are generated in adult mice, songbirds and primates, including humans. Normally, adult neurogenesis is restricted to two areas of the brain the subventricular zone, which lines the lateral ventricles, and the dentate gyrus of the hippocampal formation.[14] Although the generation of new neurons in the hippocampus is well established, the presence of true self-renewing stem cells there has been debated.[15] Under certain circumstances, such as following tissue damage in ischemia, neurogenesis can be induced in other brain regions, including the neocortex.

Neural stem cells are commonly cultured in vitro as so called neurospheres floating heterogeneous aggregates of cells, containing a large proportion of stem cells.[16] They can be propagated for extended periods of time and differentiated into both neuronal and glia cells, and therefore behave as stem cells. However, some recent studies suggest that this behaviour is induced by the culture conditions in progenitor cells, the progeny of stem cell division that normally undergo a strictly limited number of replication cycles in vivo.[17] Furthermore, neurosphere-derived cells do not behave as stem cells when transplanted back into the brain.[18]

Neural stem cells share many properties with haematopoietic stem cells (HSCs). Remarkably, when injected into the blood, neurosphere-derived cells differentiate into various cell types of the immune system.[19]

Olfactory adult stem cells have been successfully harvested from the human olfactory mucosa cells, which are found in the lining of the nose and are involved in the sense of smell.[20] If they are given the right chemical environment these cells have the same ability as embryonic stem cells to develop into many different cell types. Olfactory stem cells hold the potential for therapeutic applications and, in contrast to neural stem cells, can be harvested with ease without harm to the patient. This means they can be easily obtained from all individuals, including older patients who might be most in need of stem cell therapies.

Hair follicles contain two types of stem cells, one of which appears to represent a remnant of the stem cells of the embryonic neural crest. Similar cells have been found in the gastrointestinal tract, sciatic nerve, cardiac outflow tract and spinal and sympathetic ganglia. These cells can generate neurons, Schwann cells, myofibroblast, chondrocytes and melanocytes.[21][22]

Multipotent stem cells with a claimed equivalency to embryonic stem cells have been derived from spermatogonial progenitor cells found in the testicles of laboratory mice by scientists in Germany[23][24][25] and the United States,[26][27][28][29] and, a year later, researchers from Germany and the United Kingdom confirmed the same capability using cells from the testicles of humans.[30] The extracted stem cells are known as human adult germline stem cells (GSCs)[31]

Multipotent stem cells have also been derived from germ cells found in human testicles.[32]

To ensure self-renewal, stem cells undergo two types of cell division (see Stem cell division and differentiation diagram). Symmetric division gives rise to two identical daughter cells, both endowed with stem cell properties, whereas asymmetric division produces only one stem cell and a progenitor cell with limited self-renewal potential. Progenitors can go through several rounds of cell division before finally differentiating into a mature cell. It is believed that the molecular distinction between symmetric and asymmetric divisions lies in differential segregation of cell membrane proteins (such as receptors) between the daughter cells.

Discoveries in recent years have suggested that adult stem cells might have the ability to differentiate into cell types from different germ layers. For instance, neural stem cells from the brain, which are derived from ectoderm, can differentiate into ectoderm, mesoderm, and endoderm.[33] Stem cells from the bone marrow, which is derived from mesoderm, can differentiate into liver, lung, GI tract and skin, which are derived from endoderm and mesoderm.[34] This phenomenon is referred to as stem cell transdifferentiation or plasticity. It can be induced by modifying the growth medium when stem cells are cultured in vitro or transplanting them to an organ of the body different from the one they were originally isolated from. There is yet no consensus among biologists on the prevalence and physiological and therapeutic relevance of stem cell plasticity. More recent findings suggest that pluripotent stem cells may reside in blood and adult tissues in a dormant state.[35] These cells are referred to as "Blastomere Like Stem Cells"[36] and "very small embryonic like" "VSEL" stem cells, and display pluripotency in vitro.[35] As BLSC's and VSEL cells are present in virtually all adult tissues, including lung, brain, kidneys, muscles, and pancreas[37] Co-purification of BLSC's and VSEL cells with other populations of adult stem cells may explain the apparent pluripotency of adult stem cell populations. However, recent studies have shown that both human and murine VSEL cells lack stem cell characteristics and are not pluripotent.[38][39][40][41]

Stem cell function becomes impaired with age, and this contributes to progressive deterioration of tissue maintenance and repair.[42] A likely important cause of increasing stem cell dysfunction is age-dependent accumulation of DNA damage in both stem cells and the cells that comprise the stem cell environment.[42] (See also DNA damage theory of aging.)

Adult stem cells can, however, be artificially reverted to a state where they behave like embryonic stem cells (including the associated DNA repair mechanisms). This was done with mice as early as 2006[43] with future prospects to slow down human aging substantially. Such cells are one of the various classes of induced stem cells.

Adult stem cell research has been focused on uncovering the general molecular mechanisms that control their self-renewal and differentiation.

Adult stem cell treatments have been used for many years to successfully treat leukemia and related bone/blood cancers utilizing bone marrow transplants.[47] The use of adult stem cells in research and therapy is not considered as controversial as the use of embryonic stem cells, because the production of adult stem cells does not require the destruction of an embryo.

Early regenerative applications of adult stem cells has focused on intravenous delivery of blood progenitors known as Hematopetic Stem Cells (HSC's). CD34+ hematopoietic Stem Cells have been clinically applied to treat various diseases including spinal cord injury,[48] liver cirrhosis [49] and Peripheral Vascular disease.[50] Research has shown that CD34+ hematopoietic Stem Cells are relatively more numerous in men than in women of reproductive age group among spinal cord Injury victims.[51] Other early commercial applications have focused on Mesenchymal Stem Cells (MSCs). For both cell lines, direct injection or placement of cells into a site in need of repair may be the preferred method of treatment, as vascular delivery suffers from a "pulmonary first pass effect" where intravenous injected cells are sequestered in the lungs.[52] Clinical case reports in orthopedic applications have been published. Wakitani has published a small case series of nine defects in five knees involving surgical transplantation of mesenchymal stem cells with coverage of the treated chondral defects.[53] Centeno et al. have reported high field MRI evidence of increased cartilage and meniscus volume in individual human clinical subjects as well as a large n=227 safety study.[54][55][56][57] Many other stem cell based treatments are operating outside the US, with much controversy being reported regarding these treatments as some feel more regulation is needed as clinics tend to exaggerate claims of success and minimize or omit risks.[58]

The therapeutic potential of adult stem cells is the focus of much scientific research, due to their ability to be harvested from the parent body that is females during the delivery.[59][60][61] In common with embryonic stem cells, adult stem cells have the ability to differentiate into more than one cell type, but unlike the former they are often restricted to certain types or "lineages". The ability of a differentiated stem cell of one lineage to produce cells of a different lineage is called transdifferentiation. Some types of adult stem cells are more capable of transdifferentiation than others, but for many there is no evidence that such a transformation is possible. Consequently, adult stem therapies require a stem cell source of the specific lineage needed, and harvesting and/or culturing them up to the numbers required is a challenge.[62][63] Additionally, cues from the immediate environment (including how stiff or porous the surrounding structure/extracellular matrix is) can alter or enhance the fate and differentiation of the stem cells.[64]

Pluripotent stem cells, i.e. cells that can give rise to any fetal or adult cell type, can be found in a number of tissues, including umbilical cord blood.[65] Using genetic reprogramming, pluripotent stem cells equivalent to embryonic stem cells have been derived from human adult skin tissue.[66][67][68][69][70] Other adult stem cells are multipotent, meaning they are restricted in the types of cell they can become, and are generally referred to by their tissue origin (such as mesenchymal stem cell, adipose-derived stem cell, endothelial stem cell, etc.).[71][72] A great deal of adult stem cell research has focused on investigating their capacity to divide or self-renew indefinitely, and their potential for differentiation.[73] In mice, pluripotent stem cells can be directly generated from adult fibroblast cultures.[74]

In recent years, acceptance of the concept of adult stem cells has increased. There is now a hypothesis that stem cells reside in many adult tissues and that these unique reservoirs of cells not only are responsible for the normal reparative and regenerative processes but are also considered to be a prime target for genetic and epigenetic changes, culminating in many abnormal conditions including cancer.[75][76] (See cancer stem cell for more details.)

Adult stem cells express transporters of the ATP-binding cassette family that actively pump a diversity of organic molecules out of the cell.[77] Many pharmaceuticals are exported by these transporters conferring multidrug resistance onto the cell. This complicates the design of drugs, for instance neural stem cell targeted therapies for the treatment of clinical depression.

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Adult stem cell - Wikipedia

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

Totipotency (Lat. totipotentia, "ability for all [things]") is the ability of a single cell to divide and produce all of the differentiated cells in an organism. Spores and zygotes are examples of totipotent cells.[4]In the spectrum of cell potency, totipotency represents the cell with the greatest differentiation potential, being able to differentiate into any embryonic cell, as well as extraembryonic cells. In contrast, pluripotent cells can only differentiate into embryonic cells.[5][6]

It is possible for a all fully differentiated cell to return to a state of totipotency.[7] This conversion to totipotency is complex, not fully understood and the subject of recent research. Research in 2011 has shown that cells may differentiate not into a fully totipotent cell, but instead into a "complex cellular variation" of totipotency.[8] Stem cells resembling totipotent blastomeres from 2-cell stage embryos can arise spontaneously in mouse embryonic stem cell cultures[9][10] and also can be induced to arise more frequently in vitro through down-regulation of the chromatin assembly activity of CAF-1.[11]

The human development model is one which can be used to describe how totipotent cells arise.[12] Human development begins when a sperm fertilizes an egg and the resulting fertilized egg creates a single totipotent cell, a zygote.[13] In the first hours after fertilization, this zygote divides into identical totipotent cells, which can later develop into any of the three germ layers of a human (endoderm, mesoderm, or ectoderm), or into cells of the placenta (cytotrophoblast or syncytiotrophoblast). After reaching a 16-cell stage, the totipotent cells of the morula differentiate into cells that will eventually become either the blastocyst's Inner cell mass or the outer trophoblasts. Approximately four days after fertilization and after several cycles of cell division, these totipotent cells begin to specialize. The inner cell mass, the source of embryonic stem cells, becomes pluripotent.

Research on Caenorhabditis elegans suggests that multiple mechanisms including RNA regulation may play a role in maintaining totipotency at different stages of development in some species.[14] Work with zebrafish and mammals suggest a further interplay between miRNA and RNA-binding proteins (RBPs) in determining development differences.[15]

In cell biology, pluripotency (Lat. pluripotentia, "ability for many [things]")[16] refers to a stem cell that has the potential to differentiate into any of the three germ layers: endoderm (interior stomach lining, gastrointestinal tract, the lungs), mesoderm (muscle, bone, blood, urogenital), or ectoderm (epidermal tissues and nervous system).[17] However, cell pluripotency is a continuum, ranging from the completely pluripotent cell that can form every cell of the embryo proper, e.g., embryonic stem cells and iPSCs (see below), to the incompletely or partially pluripotent cell that can form cells of all three germ layers but that may not exhibit all the characteristics of completely pluripotent cells.

Induced pluripotent stem cells, commonly abbreviated as iPS cells or iPSCs, are a type of pluripotent stem cell artificially derived from a non-pluripotent cell, typically an adult somatic cell, by inducing a "forced" expression of certain genes and transcription factors.[18] These transcription factors play a key role in determining the state of these cells and also highlights the fact that these somatic cells do preserve the same genetic information as early embryonic cells.[19] The ability to induce cells into a pluripotent state was initially pioneered in 2006 using mouse fibroblasts and four transcription factors, Oct4, Sox2, Klf4 and c-Myc;[20] this technique, called reprogramming, earned Shinya Yamanaka and John Gurdon the Nobel Prize in Physiology or Medicine 2012.[21] This was then followed in 2007 by the successful induction of human iPSCs derived from human dermal fibroblasts using methods similar to those used for the induction of mouse cells.[22] These induced cells exhibit similar traits to those of embryonic stem cells (ESCs) but do not require the use of embryos. Some of the similarities between ESCs and iPSCs include pluripotency, morphology, self-renewal ability, a trait that implies that they can divide and replicate indefinitely, and gene expression.[23]

Epigenetic factors are also thought to be involved in the actual reprogramming of somatic cells in order to induce pluripotency. It has been theorized that certain epigenetic factors might actually work to clear the original somatic epigenetic marks in order to acquire the new epigenetic marks that are part of achieving a pluripotent state. Chromatin is also reorganized in iPSCs and becomes like that found in ESCs in that it is less condensed and therefore more accessible. Euchromatin modifications are also common which is also consistent with the state of euchromatin found in ESCs.[23]

Due to their great similarity to ESCs, iPSCs have been of great interest to the medical and research community. iPSCs could potentially have the same therapeutic implications and applications as ESCs but without the controversial use of embryos in the process, a topic of great bioethical debate. In fact, the induced pluripotency of somatic cells into undifferentiated iPS cells was originally hailed as the end of the controversial use of embryonic stem cells. However, iPSCs were found to be potentially tumorigenic, and, despite advances,[18] were never approved for clinical stage research in the United States. Setbacks such as low replication rates and early senescence have also been encountered when making iPSCs,[24] hindering their use as ESCs replacements.

Additionally, it has been determined that the somatic expression of combined transcription factors can directly induce other defined somatic cell fates (transdifferentiation); researchers identified three neural-lineage-specific transcription factors that could directly convert mouse fibroblasts (skin cells) into fully functional neurons.[25] This result challenges the terminal nature of cellular differentiation and the integrity of lineage commitment; and implies that with the proper tools, all cells are totipotent and may form all kinds of tissue.

Some of the possible medical and therapeutic uses for iPSCs derived from patients include their use in cell and tissue transplants without the risk of rejection that is commonly encountered. iPSCs can potentially replace animal models unsuitable as well as in vitro models used for disease research.[26]

Recent findings with respect to epiblasts before and after implantation have produced proposals for classifying pluripotency into two distinct phases: "naive" and "primed".[27] The baseline stem cells commonly used in science that are referred as Embryonic stem cells (ESCs) are derived from a pre-implantation epiblast; such epiblast is able to generate the entire fetus, and one epiblast cell is able to contribute to all cell lineages if injected into another blastocyst. On the other hand, several marked differences can be observed between the pre- and post-implantation epiblasts, such as their difference in morphology, in which the epiblast after implantation changes its morphology into a cup-like shape called the "egg cylinder" as well as chromosomal alteration in which one of the X-chromosomes under random inactivation in the early stage of the egg cylinder, known as X-inactivation.[28] During this development, the egg cylinder epiblast cells are systematically targeted by Fibroblast growth factors, Wnt signaling, and other inductive factors via the surrounding yolk sac and the trophoblast tissue,[29] such that they become instructively specific according to the spatial organization.[30] Another major difference that was observed, with respect to cell potency, is that post-implantation epiblast stem cells are unable to contribute to blastocyst chimeras,[31] which distinguishes them from other known pluripotent stem cells. Cell lines derived from such post-implantation epiblasts are referred to as epiblast-derived stem cells which were first derived in laboratory in 2007; despite their nomenclature, that both ESCs and EpiSCs are derived from epiblasts, just at difference phases of development, and that pluripotency is still intact in the post-implantation epiblast, as demonstrated by the conserved expression of Nanog, Fut4, and Oct-4 in EpiSCs,[32] until somitogenesis and can be reversed midway through induced expression of Oct-4.[33]

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

New research related to multipotent cells suggests that multipotent cells may be capable of conversion into unrelated cell types. In another case, human umbilical cord blood stem cells were converted into human neurons.[34] Research is also focusing on converting multipotent cells into pluripotent cells.[35]

Multipotent cells are found in many, but not all human cell types. Multipotent cells have been found in cord blood,[36] adipose tissue,[37] cardiac cells,[38] bone marrow, and mesenchymal stem cells (MSCs) which are found in the third molar.[39]

MSCs may prove to be a valuable source for stem cells from molars at 810 years of age, before adult dental calcification. MSCs can differentiate into osteoblasts, chondrocytes, and adipocytes.[40]

In biology, oligopotency is the ability of progenitor cells to differentiate into a few cell types. It is a degree of potency. Examples of oligopotent stem cells are the lymphoid or myeloid stem cells.[2]A lymphoid cell specifically, can give rise to various blood cells such as B and T cells, however, not to a different blood cell type like a red blood cell.[41] Examples of progenitor cells are vascular stem cells that have the capacity to become both endothelial or smooth muscle cells.

In cell biology, a unipotent cell is the concept that one stem cell has the capacity to differentiate into only one cell type. It is currently unclear if true unipotent stem cells exist. Hepatoblasts, which differentiate into hepatocytes (which constitute most of the liver) or cholangiocytes (epithelial cells of the bile duct), are bipotent.[42] A close synonym for unipotent cell is precursor cell.

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Where do stem cells come from? Learn the basics of master cells to better understand their therapeutic potential.

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Where do stem cells come from? You have probably heard of thewonders of stem cell therapy. Not only do stem cells make research for future scientific breakthroughs possible, but they also provide the basis for many medical treatments today. So, where exactly are they from, and how are they different from regular cells? The answer depends on the types of stem cells in question.

There are two main types of stem cells adult and embryonic:

Beyond the two broader categories, there are sub-categories. Each has its own characteristics. For researchers, the different types of stem cells serve specific purposes.

Many tissues throughout the adult human body contain stem cells. Scientists previously believed adult stem cells to be inferior to human embryonic stem cells for therapeutic purposes. Theydid not believe adult stem cells to be as versatile as embryonic stem cells (ESCs), because they are not capable of becoming all 200 cell types within the human body.

While this theoryhas notbeen entirely disproved, encouraging evidence suggests that adult stem cells can develop into a variety of new types of cells. They can also affect repair through other mechanisms.

In August 2017, the number of stem cell publications registered in PubMed, a government database, surpassed 300,000. Stem cells are also being explored in over 4,600 cell therapy clinical trials worldwide. Some of the earliest forms of adult stem cell use include bone marrow and umbilical cord blood transplantation.

It should be noted that while the term adult stem cell is used for this type of cell, it is not descriptive of age, because adult stem cells can come from children. The term simply helps to differentiate stem cells derived from living humans as opposed to embryonic stem cells.

Embryonic stem cells are controversial because they are made from embryos that are created but not used by fertility clinics.

Because adult stem cells are somewhat limited in the cell types they can become, scientists developed a way to genetically reprogram cells into what is called an inducedpluripotent stem cell or iPS cell. In creating inducedpluripotent stem cells, researchers hope to blend the usefulness of adult stem cells with the promise of embryonic stem cells.

Both embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) are known as pluripotent stem cells.

Pluripotent stem cells are a type of cell that has the capacity to divide indefinitely and create any cell found within the three germ layers of an organism: ectoderm (cells forming the skin and nervous system), endoderm (cells forming pancreas, liver, endocrine gland, and gastrointestinal and respiratory tracts), and mesoderm (cells forming connective tissues, and other related tissues, muscles, bones, most of the circulatory system, and cartilage).

Embryonic stem cells can grow into a much wider range of cell types, but they also carry the risk of immune system rejection in patients. In contrast, adult stem cells are more plentiful, easier to harvest, and less controversial.

Embryonic stem cells come from embryos harvested shortly after fertilization (within 4-5 days). These cells are made when the blastocysts inner cell mass is transferred into a culture medium, allowing them to develop.

At 5-6 days post-fertilization, the cells within the embryo start to specialize. At this time, they no longer are able to become all of the cell types within the human body. They are no longer pluripotent.

Because they are pluripotent, embryonic stem cells can be used to generate healthy cells for disease patients. For example, they can be grown into heart cells known as cardiomyocytes. These cells may have the potential to be injected into an ailing patients heart.

Harvesting stem cells from embryos is controversial, so there are guidelines created by the National Institutes of Health (NIH) that allow the public to understand what practices are not allowed.

Scientists can harvest perinatal stem cells from a variety of tissues, but the most common sources include:

The umbilical cord attaches a mother to her fetus. It is removed after birth and is a valuable source of stem cells. The blood it contains is rich in hematopoietic stem cells (HSC). It also contains smaller quantities of another cell type known as mesenchymal stem cells (MSCs).

The placenta is a large organ that acts as a connector between the mother and the fetus. Both placental blood and tissue are also rich in stem cells.

Finally, there is amniotic fluid surrounding a baby while it is in utero. It can be harvested if a pregnant woman needs a specialized kind of test known as amniocentesis. Both amniotic fluid and tissue contain stem cells, too.

Adult stem cells are usually harvested in one of three ways:

The blood draw, known as peripheral blood stem cell donation, extracts the stem cells directly from a donors bloodstream. The bone marrow stem cells come from deep within a bone often a flat bone such as the hip. Tissue fat is extracted from a fatty area, such as the waist.

Embryonic donations are harvested from fertilized human eggs that are less than five days old. The embryos are not grown within a mothers or surrogates womb, but instead, are multiplied in a laboratory. The embryos selected for harvesting stem cell are created within invitro fertilization clinics but are not selected for implantation.

Amniotic stem cells can be harvested at the same time that doctors use a needle to withdraw amniotic fluid during a pregnant womans amniocentesis. The same fluid, after being tested to ensure the babys health, can also be used to extract stem cells.

As mentioned, there is another source for stem cells the umbilical cord. Blood cells from the umbilical cord can be harvested after a babys birth. Cells can also be extracted from the postpartumhuman placenta, which is typically discarded as medical waste following childbirth.

The umbilical cord and the placenta are non-invasive sources of perinatal stem cells.

People who donate stem cells through the peripheral blood stem cell donor procedure report it to be a relativelypainless procedure. Similar to giving blood, the procedure takes about four hours. At a clinic or hospital, an able medical practitioner draws the blood from the donors vein in one of his arms using a needle injection. The technician sends the drawn blood into a machine, which extracts the stem cells. The blood is then returned to the donors body via a needle injected into the other arm. Some patients experience cramping or dizziness, but overall, its considered a painless procedure.

If a blood stem cell donor has a problem with his or her veins, a catheter may be injected in the neck or chest. The donor receives local anesthesia when a catheter-involved donation occurs.

During a bone marrow stem cell donor procedure, the donor is put under heavy sedation in an operating room. The hip is often the site chosen to harvest the bone marrow. More of the desired red marrow is found in flat bones, such as those in the pelvic region. The procedure takes up to two hours, with several extractions made while the patient is sedated. Although the procedure is painless due to sedation, recovery can take a couple of weeks.

Bone marrow stem cell donation takes a toll on the donorbecause it involves the extraction of up to 10 percent of the donors marrow. During the recovery period, the donors body gradually replenishes the marrow. Until that happens, the donor may feel fatigued and sore.

Some clinics offer regenerative and cosmetic therapies using the patients own stem cells derived from the fat tissue located on the sides of the waistline. Considered a simple procedure, clinics do this for therapeutic reasons or as a donation for research.

Stem cells differ from the trillions of other cells in your body. In fact, stem cells make up only a small fraction of the total cells in your body. Some people have a higher percentage of stem cells than others. But, stem cells are special because they are the mothers from which specialized cells grew and developed within us. When these cells divide, they become daughters. Some daughter cells simply self-replicate, while others form new kinds of cells altogether. This is the main way stem cells differ from other body cells they are the only ones capable of generating new cells.

The ways in which stem cells can directly treat patients grow each year. Regenerative medicine now relies heavily on stem cell applications. This type of treatment replaces diseased cells with new, healthy ones generated through donor stem cells. The donor can be another person or the patient themselves.

Sometimes, stem cells also exert therapeutic effects by traveling through the bloodstream to sites that need repair or by impacting their micro-environment through signaling mechanisms.

Some types of adult stem cells, like mesenchymal stem cells (MSCs), are well-known for exerting anti-inflammatory and anti-scarring effects. MSCs can also positively impact the immune system.

Conditions and diseases which stem cell regeneration therapy may help include Alzheimers disease, Parkinsons disease, and multiple sclerosis (MS). Heart disease, certain types of cancer, and stroke victims may also benefit in the future. Stem cell transplant promises advances in treatment for diabetes, spinal cord injury, severe burns, and osteoarthritis.

Researchers also utilize stem cells to test new drugs. In this case, an unhealthy tissue replicates into a larger sample. This method enables researchers to test various therapies on a diseased sample, rather than on an ailing patient.

Stem cell research also allows scientists to study how both healthy and diseased tissue grows and mutates under various conditions. They do this by harvesting stem cells from the heart, bones, and other body areas and studying them under intensive laboratory conditions. In this way, they get a better understanding of the human body, whether healthy or sick.

With the following stem cell transplant benefits, its not surprising people would like to try the therapy as another treatment option.

Physicians harvest stem cell from either the patient or a donor. For an autologous transplant, there is no risk of transferring any disease from another person. For an allogeneic transplant, the donor is meticulously screened before the therapy to make sure they are compatible with the patient and have healthy sources of stem cells.

One common and serious problem of transplants is the risk of rejecting the transplanted organs, tissues, stem cells, and others. With autologous stem cell therapy, the risk is avoided primarily because it comes from the same person.

Because stem cell transplants are typically done through infusion or injection, the complex and complicated surgical procedure is avoided. Theres no risk of accidental cuts and scarring post-surgery.

Recovery time from surgeries and other types of treatments is usually time-consuming. With stem cell therapy, it could only take about 3 months or less to get the patient back to their normal state.

As the number of stem cell treatments dramatically grew over the years, its survival rate also increased. A study published in the Journal of Clinical Oncology showed there was a significant increase in survival rate over 12 years among participants of the study. The study analyzed results from over 38,000 stem cell transplants on patients with blood cancers and other health conditions.

One hundred days following transplant, the researchers observed an improvement in the survival rate of patients with myeloid leukemia. The significant improvements we saw across all patient and disease populations should offer patients hope and, among physicians, reinforce the role of blood stem cell transplants as a curative option for life-threatening blood cancers and other diseases.

With the information above, people now have a better understanding of the answer to the question Where do stem cells come from? Stem cells are a broad topic to comprehend, and its better to go back to its basics to learn its mechanisms. This way, a person can have a piece of detailed knowledge about these master cells from a scientific perspective.

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Where Do Stem Cells Come From? | Basics Of Stem Cell Therapy

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Where Do Stem Cells Come From? | Basics Of Stem Cell ...

Stem cells are powerful, adaptable cells that can be used to promote healing and reverse damage. Stem cells are found in various places within the human body, but the purest stem cells are found in the umbilical cord.

Stem cells can be used in treatments for many different types of diseases. One of the main places young stem cells are found is in cord blood, which can be stored at birth and saved for future use if needed. Stem cells are also found in other places in the human body, including blood and bone marrow.

Regenerative transplants use stem cells from three main sources:

Bone marrow is tissue located in the center of your bones, making healthy blood cells that strengthen your immune system and fight off outside infections. A large amount of cells are located in bone marrow, and doctors frequently use hip bone marrow for most transplants, since the stem cells in this area are the most plentiful.

When doctors remove bone marrow, the patient receives anesthesia. This puts them to sleep and numbs any pain from the surgery. Doctors then insert a large needle, and pull the liquid marrow out. Once enough bone marrow is harvested, the solution is filtered and cryogenically frozen.

When a patient needs bone marrow for a transplant, stem cells are thawed and injected into the bloodstream. The cells then make their way to the bone marrow, and start producing new blood cells this process usually takes a few weeks.

While most people have a small amount of stem cells in their bloodstream, donors produce more stem cells after taking growth factor hormones. Doctors give these medications a few days before stem cell harvesting, which makes the bone marrow push more cells into the bloodstream.

During the harvesting procedure, doctors use a catheter to draw out blood. The blood moves through a machine, which separates stem cells and allows these cells to be put into storage. This process takes a few hours, and may be repeated over several days in order for doctors to get enough stem cells.

Stem cells are injected into the veins during a peripheral blood transplant, and naturally work their way to the bone marrow. Once there, the new cells start increasing healthy blood count. Compared to bone marrow transplants, cells from peripheral blood are usually faster, creating new blood cells within two weeks.

Umbilical cord blood contains a large amount of stem cells. If parents sign up for personalized storage or donation, medical staff will remove stem cells from the umbilical cord and placenta. The blood is then cryogenically frozen, and put into long-term storage.

While the stem cell count is smaller during a cord blood transplant, these cells multiply quickly, and researchers are studying new methods to increase cells naturally. Compared to bone marrow, cord blood cells multiply faster and dont require an exact match type to complete a successful transplant. Some techniques medical experts are testing to increase the amount of stem cells include:

While all three stem cell sources are used in similar procedures, they each have advantages and drawbacks. Bone marrow transplants are the traditional form of therapy, but peripheral blood cells are becoming more popular, since doctors often get more stem cells from the bloodstream.

The procedure for peripheral blood harvesting is easier on the patient than a bone marrow transplant, and stem cell transplants are faster. However, the chances for graft-versus-host disease, where donated cells attack the patients body, are much higher after a peripheral blood transplant.

Cord blood transplants are the least invasive, since they come from an external source the umbilical cord.

The biggest advantage for cord blood is the immaturity of the cells, which means transplants do not require an exact match. For bone marrow and peripheral blood transplants, donors need to match the patients cellular structure. However, cord blood cells can adapt to a wide variety of patients, and dont require donor matching. Chances for graft-versus-host disease are also much lower for cord blood transplants.

Patients and doctors can avoid graft-versus-host disease, and other dangerous side effects, by using HLA matching.

Multipotent stem cells develop into organ system cells, and are made from two different types of cells:

HSCs can become any type of blood cell or cellular blood component inside the body, including white blood cells and red blood cells. These cells are found in umbilical cord blood and are multipotent, which means they can develop into more than one cell type.

This cell type has been used in over 1 million patient transplants around the world.

MSCs can turn into bone, cartilage, fat tissue, and more. Although they are associated with bone marrow, these cells are also found in umbilical cord blood. These cells can function as connective tissue, which connects vital organs inside the body. Like HSCs, MSCs are multipotent.

Pluripotent cells can replace any type of cellular system in the body. Cord blood contains a rich variety of pluripotent stem cells, which allows treatment for a large amount of patients.

iPS cells are artificially-made pluripotent stem cells. This technique allows medical staff to create additional pluripotent cells, which will increase treatment options for patients using stem cell therapy in the near future.

ES cells are pluripotent, and similar to iPS cells, but come from an embryo. However, this kills the fertilized baby inside the embryo. This type of cell also has a high chance for graft-versus-host disease, when transplanted cells attack the patients body.

Your adult cells have one disadvantage to cord blood cells they cannot change their cell type. When stem cells from cord blood and tissue are transplanted, they adjust to fit the individual patient and replace damaged cells. Adult stem cells are also older, which means they have been exposed to disease, and may damage patients after the transplant. Compared to cord blood cells, adult cells have a higher chance for graft-versus-host disease.

Cord blood contains a wide variety of cell types, but there are different stem cell sources available to patients in need of a transplant.

Last Updated on February 15th, 2017

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Stem Cells Used in Cord Blood Treatments

How are the donors stem cells matched to the patients stem cells in allogeneic or syngeneic transplantation?

To minimize potential side effects, doctors most often use transplanted stem cells that match the patients own stem cells as closely as possible. People have different sets of proteins, called human leukocyte-associated (HLA) antigens, on the surface of their cells. The set of proteins, called the HLA type, is identified by a special blood test.

In most cases, the success of allogeneic transplantation depends in part on how well the HLA antigens of the donors stem cells match those of the recipients stem cells. The higher the number of matching HLA antigens, the greater the chance that the patients body will accept the donors stem cells. In general, patients are less likely to develop a complication known as graft-versus-host disease (GVHD) if the stem cells of the donor and patient are closely matched.

Close relatives, especially brothers and sisters, are more likely than unrelated people to be HLA-matched. However, only 25 to 35 percent of patients have an HLA-matched sibling. The chances of obtaining HLA-matched stem cells from an unrelated donor are slightly better, approximately 50 percent. Among unrelated donors, HLA-matching is greatly improved when the donor and recipient have the same ethnic and racial background. Although the number of donors is increasing overall, individuals from certain ethnic and racial groups still have a lower chance of finding a matching donor. Large volunteer donor registries can assist in finding an appropriate unrelated donor.

Because identical twins have the same genes, they have the same set of HLA antigens. As a result, the patients body will accept a transplant from an identical twin. However, identical twins represent a small number of all births, so syngeneic transplantation is rare.

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Blood-Forming Stem Cell Transplants - National Cancer Institute

Tissue-specific stem cells

Tissue-specific stem cells (also referred to assomaticoradultstem cells) are more specialized than embryonic stem cells. Typically, these stem cells can generate different cell types for the specific tissue or organ in which they live.

For example, blood-forming (orhematopoietic) stem cells in the bone marrow can give rise to red blood cells, white blood cells and platelets. However, blood-forming stem cells dont generate liver or lung or brain cells, and stem cells in other tissues and organs dont generate red or white blood cells or platelets.

Some tissues and organs within your body contain small caches of tissue-specific stem cells whose job it is to replace cells from that tissue that are lost in normal day-to-day living or in injury, such as those in your skin, blood, and the lining of your gut.

Tissue-specific stem cells can be difficult to find in the human body, and they dont seem to self-renew in culture as easily as embryonic stem cells do. However, study of these cells has increased our general knowledge about normal development, what changes in aging, and what happens with injury and disease.

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Types of Stem Cells A Closer Look at Stem Cells

Stem cells differ from other kinds of cells in the body. All stem cellsregardless of their sourcehave three general properties: they are capable of dividing and renewing themselves for long periods; they are unspecialized; and they can give rise to specialized cell types.

Stem cells are capable of dividing and renewing themselves for long periods. Unlike muscle cells, blood cells, or nerve cellswhich do not normally replicate themselvesstem cells may replicate many times, or proliferate. A starting population of stem cells that proliferates for many months in the laboratory can yield millions of cells. If the resulting cells continue to be unspecialized, like the parent stem cells, the cells are said to be capable of long-term self-renewal.

Scientists are trying to understand two fundamental properties of stem cells that relate to their long-term self-renewal:

Discovering the answers to these questions may make it possible to understand how cell proliferation is regulated during normal embryonic development or during the abnormal cell division that leads to cancer. Such information would also enable scientists to grow embryonic and non-embryonic stem cells more efficiently in the laboratory.

The specific factors and conditions that allow stem cells to remain unspecialized are of great interest to scientists. It has taken scientists many years of trial and error to learn to derive and maintain stem cells in the laboratory without them spontaneously differentiating into specific cell types. For example, it took two decades to learn how to grow human embryonic stem cells in the laboratory following the development of conditions for growing mouse stem cells. Likewise, scientists must first understand the signals thatenable a non-embryonic (adult)stem cell population to proliferate and remain unspecialized before they will be able to grow large numbers of unspecialized adult stem cells in the laboratory.

Stem cells are unspecialized. One of the fundamental properties of a stem cell is that it does not have any tissue-specific structures that allow it to perform specialized functions. For example, a stem cell cannot work with its neighbors to pump blood through the body (like a heart muscle cell), and it cannot carry oxygen molecules through the bloodstream (like a red blood cell). However, unspecialized stem cells can give rise to specialized cells, including heart muscle cells, blood cells, or nerve cells.

Stem cells can give rise to specialized cells. When unspecialized stem cells give rise to specialized cells, the process is called differentiation. While differentiating, the cell usually goes through several stages, becoming more specialized at each step. Scientists are just beginning to understand the signals inside and outside cells that trigger each step of the differentiation process. The internal signals are controlled by a cell's genes, which are interspersed across long strands of DNA and carry coded instructions for all cellular structures and functions. The external signals for cell differentiation include chemicals secreted by other cells, physical contact with neighboring cells, and certain molecules in the microenvironment. The interaction of signals during differentiation causes the cell's DNA to acquire epigenetic marks that restrict DNA expression in the cell and can be passed on through cell division.

Many questions about stem cell differentiation remain. For example, are the internal and external signals for cell differentiation similar for all kinds of stem cells? Can specific sets of signals be identified that promote differentiation into specific cell types? Addressing these questions may lead scientists to find new ways to control stem cell differentiation in the laboratory, thereby growing cells or tissues that can be used for specific purposes such as cell-based therapies or drug screening.

Adult stem cells typically generate the cell types of the tissue in which they reside. For example, a blood-forming adult stem cell in the bone marrow normally gives rise to the many types of blood cells. It is generally accepted that a blood-forming cell in the bone marrowwhich is called a hematopoietic stem cellcannot give rise to the cells of a very different tissue, such as nerve cells in the brain. Experiments over the last several years have purported to show that stem cells from one tissue may give rise to cell types of a completely different tissue. This remains an area of great debate within the research community. This controversy demonstrates the challenges of studying adult stem cells and suggests that additional research using adult stem cells is necessary to understand their full potential as future therapies.

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