The Promise of Stem Cells

Studying stem cells will help us understand how they transform into the dazzling array of specialized cells that make us what we are. Some of the most serious medical conditions, such as cancer and birth defects, are due to problems that occur somewhere in this process. A better understanding of normal cell development will allow us to understand and perhaps correct the errors that cause these medical conditions.

Another potential application of stem cells is making cells and tissues for medical therapies. Today, donated organs and tissues are often used to replace those that are diseased or destroyed. Unfortunately, the number of people needing a transplant far exceeds the number of organs available for transplantation. Pluripotent stem cells offer the possibility of a renewable source of replacement cells and tissues to treat a myriad of diseases, conditions, and disabilities including Parkinson's disease, amyotrophic lateral sclerosis, spinal cord injury, burns, heart disease, diabetes, and arthritis.

Scientists have been able to do experiments with human embryonic stem cells (hESC) since 1998, when a group led by Dr. James Thomson at the University of Wisconsin developed a technique to isolate and grow the cells. Although hESCs are thought to offer potential cures and therapies for many devastating diseases, research using them is still in its basic stages. hESCs are thought to offer potential cures and therapies for many devastating diseases, and we are now seeing the first clinical trials using cells derived from hESCs.

The NIH funded its first basic research study on hESCs in 2002. Since that time, biotechnology companies have built upon those basic foundations to begin developing stem cell-based human therapies. There are currently two active clinical trials using cells derived from human embryonic stem cells, both being conducted by a biotechnology company called ACT. The company has laboratories in Marlborough, Massachusetts and corporate offices in Santa Monica, California. ACT has begun enrolling patients for Phase I (safety and tolerability) clinical trials of two hESC-derived stem cell products:

In January, 2012, the investigators published a preliminary report on the first two patients treated with hESC-derived cells: http://www.ncbi.nlm.nih.gov/pubmed/22281388. A third patient was treated on April 20, 2012.

Late in 2007, scientists reported that they had been able to reprogram adult human skin cells to behave like hESCs. This type of stem cells is known as induced pluripotent stem cells, or iPSCs. Since these first reports, researchers have rapidly improved the techniques to generate iPSCs, creating a powerful new way to "de-differentiate" cells whose developmental fates were thought to be determined. In July 2013, Japans health minister approved the first clinical trial using cells derived from iPSCs. Masayo Takahashiin Kobe, Japan will use the cells to attempt to treat a form of blindness - age-related macular degeneration.

Bone marrow contains blood-forming stem cells (hematopoietic stem cells) that have been used for decades to treat blood cancers and other blood disorders. Umbilical cord blood is another source of hematopoietic stem cells that is being used in treatment. You can see a list of diseases that may currently be treated with hematopoietic stem cells at the website of the National Marrow Donor Program. You may also search for clinical trials testing "bone marrow stem cells" or "umbilical cord blood" on the ClinicalTrials.gov website.

A biotechnology company called Neuralstem (corporate headquarters in Rockville, Maryland) is conducting a clinical trial testing the use of human spinal cord stem cells to treat Amyotrophic Lateral Sclerosis (ALS), also known as Lou Gehrigs Disease. The company obtained FDA approval to conduct a Phase I trial (safety and tolerability study) and began enrolling patients in January 2010. Twelve participants have received lumbar transplants, and in March 2012, the second participant received an injection in the cervial region. Details about this trial are listed on the ClinicalTrials.gov website.

Osiris Therapeutics (Columbia, Maryland) is conducting three different Phase 2 clinical trials with a product from adult mesenchymal cells (called Prochymal). The three trials are for:

See the article here:
Stem Cells and Diseases [Stem Cell Information]

CIRM funds a variety of research projects focused on finding a treatment for people with spinal cord injury. These projects range from basic work understanding how nerve cells are damaged in these injuries to projects trying move therapies into clinical trials.

If you want to learn more about CIRM funding decisions or make a comment directly to our board, join us at a public meeting. You can find agendas for upcoming public meetings on our meetings page.

Learn more about stem cell research: Stem Cell Basics Primer | Stem Cell Videos | What We Fund

Find clinical trials: CIRM does not track stem cell clinical trials. If you or a family member is interested in participating in a clinical trial, please see the national trial database to find a trial near you: clinicaltrials.gov

About 250,000 people in the U.S. live with spinal cord injuries. Half of those are quadriplegic, with the paralysis impacting all four limbs to some extent. For those individuals the lifetime cost of managing their condition is estimated to be between $2 million and $3 million.

Spinal cord injury became the first condition targeted in a human clinical trial using cells made from embryonic stem cells. That trial, begun by Geron in 2010 and based on the findings of a team CIRM currently funds, was later cancelled by Geron for financial reasons. By the time of the cancellation five patients around the country had been enrolled in the study, including two at Stanford, who entered the trial during a period when CIRM funded Geron. Those patients continue to be followed to learn as much as possible about this approach.

Californias stem cell agency retains many grants for research to move potential spinal cord injury therapies forward (the full list is below). Much of this work focuses on trying to determine which type of nerve cell is the best one to transplant, and deciding which type of stem cell is the best starting point for making those cells. Other research is trying to see if these transplanted cells become part of the existing nerve system, helping create new pathways that can transmit nerve signals to muscles. The researchers are also looking at ways to try and improve the ability of these transplanted cells to become part of the nerve system.

One obstacle that some teams are trying to overcome is the tendency of the scar at the site of injury to block the growth of these transplanted cells. One group is trying to overcome that by combining stem cells with synthetic scaffolds that can be placed at the site of injury, to help the cells bridge the scar and restore signals. In animal models this combination has resulted in an increase in mobility compared to stem cell grafts alone.

Progress and Promise toward a stem cell-based therapy for spinal cord injury

Total:

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Spinal Cord Injury Fact Sheet | California's Stem Cell Agency

This article is about the medical therapy. For the cell type, see Stem cell.

Stem cell therapy is an intervention strategy that introduces new adult stem cells into damaged tissue in order to treat disease or injury. Many medical researchers believe that stem cell treatments have the potential to change the face of human disease and alleviate suffering.[1] The ability of stem cells to self-renew and give rise to subsequent generations with variable degrees of differentiation capacities,[2] offers significant potential for generation of tissues that can potentially replace diseased and damaged areas in the body, with minimal risk of rejection and side effects.

A number of stem cell therapies exist, but most are at experimental stages, costly or controversial,[3] with the notable exception of bone-marrow transplantation.[citation needed] Medical researchers anticipate that adult and embryonic stem cells will soon be able to treat cancer, Type 1 diabetes mellitus, Parkinson's disease, Huntington's disease, Celiac disease, cardiac failure, muscle damage and neurological disorders, and many others.[4] Nevertheless, before stem cell therapeutics can be applied in the clinical setting, more research is necessary to understand stem cell behavior upon transplantation as well as the mechanisms of stem cell interaction with the diseased/injured microenvironment.[4]

For over 30 years, bone-marrow, and more recently, umbilical-cord blood stem cells, have been used to treat cancer patients with conditions such as leukemia and lymphoma.[5][6] During chemotherapy, most growing cells are killed by the cytotoxic agents. These agents, however, cannot discriminate between the leukaemia or neoplastic cells, and the hematopoietic stem cells within the bone marrow. It is this side effect of conventional chemotherapy strategies that the stem cell transplant attempts to reverse; a donor's healthy bone marrow reintroduces functional stem cells to replace the cells lost in the host's body during treatment.

Stroke and traumatic brain injury lead to cell death, characterized by a loss of neurons and oligodendrocytes within the brain. Healthy adult brains contain neural stem cells which divide to maintain general stem cell numbers, or become progenitor cells. In healthy adult animals, progenitor cells migrate within the brain and function primarily to maintain neuron populations for olfaction (the sense of smell). In pregnancy and after injury, this system appears to be regulated by growth factors and can increase the rate at which new brain matter is formed.[citation needed] Although the reparative process appears to initiate following trauma to the brain, substantial recovery is rarely observed in adults, suggesting a lack of robustness.[7]

Stem cells may also be used to treat brain degeneration, such as in Parkinson's and Alzheimer's disease.[8][9]

Pharmacological activation of an endogenous population of neural stem cells / neural precursor cells by soluble factors has been reported to induce powerful neuroprotection and behavioral recovery in adult rat models of neurological disorder through a signal transduction pathway involving the phosphorylation of STAT3 on the serine residue and subsequent Hes3 expression increase (STAT3-Ser/Hes3 Signaling Axis).[10][11][12]

Stem cell technology gives hope of effective treatment for a variety of malignant and non-malignant diseases through the rapid developing field that combines the efforts of cell biologists, geneticists and clinicians. Stem cells are defined as totipotent progenitor cells capable of self-renewal and multi-lineage differentiation. Stem cells survive well and show steady division in culture which then causes them the ideal targets for vitro manipulation. Research into solid tissue stem cells has not made the same progress as haematopoietic stem cells because of the difficulty of reproducing the necessary and precise 3D arrangements and tight cell-cell and cell-extracellular matrix interactions that exist in solid organs. Yet, the ability of tissue stem cells to assimilate into the tissue cytoarchitecture under the control of the host microenvironment and developmental cues, makes them ideal for cell replacement therapy. [3] [13]

The development of gene therapy strategies for treatment of intra-cranial tumours offers much promise, and has shown to be successful in the treatment of some dogs;[14] although research in this area is still at an early stage. Using conventional techniques, brain cancer is difficult to treat because it spreads so rapidly. Researchers at the Harvard Medical School transplanted human neural stem cells into the brain of rodents that received intracranial tumours. Within days, the cells migrated into the cancerous area and produced cytosine deaminase, an enzyme that converts a non-toxic pro-drug into a chemotheraputic agent. As a result, the injected substance was able to reduce the tumor mass by 81 percent. The stem cells neither differentiated nor turned tumorigenic.[15]

Some researchers believe that the key to finding a cure for cancer is to inhibit proliferation of cancer stem cells. Accordingly, current cancer treatments are designed to kill cancer cells. However, conventional chemotherapy treatments cannot discriminate between cancerous cells and others. Stem cell therapies may serve as potential treatments for cancer.[16] Research on treating lymphoma using adult stem cells is underway and has had human trials. Essentially, chemotherapy is used to completely destroy the patients own lymphocytes, and stem cells injected, eventually replacing the immune system of the patient with that of the healthy donor.

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Stem cell therapy - Wikipedia, the free encyclopedia

Results from a ground-breaking Cedars-Sinai Heart Institute clinical trial show that an infusion of cardiac stem cells helps damaged hearts regrow healthy muscle.

The first-in-man clinical trial, based on technologies and discoveries made by Eduardo Marbn, MD, PhD, and led by Raj Makkar, MD, explored the safety of harvesting, growing and giving patients their own cardiac stem cells to repair heart tissue injured by heart attack.

The studys findings, published in The Lancet, show that heart attack patients who received stem cell treatment demonstrated a significant reduction in the size of the scar left on the heart muscle; this is a pioneering stem cell result, says Marban, who notes the study shows actual regeneration of tissues. With support from the California Institute for Regenerative Medicine, the Heart Institute team is now planning future clinical trials to treat advanced heart disease patients with stem cells.

The process to grow cardiac-derived stem cells involved in the study was developed earlier by Marbn when he was on the faculty of Johns Hopkins University. The university has filed for a patent on that intellectual property, and has licensed it to a company in which Marbn has a financial interest. No funds from that company were used to support the clinical study. All funding was derived from the National Institutes of Health and Cedars-Sinai Medical Center.

Since the Cedars-Sinai team completed the worlds first cardiac stem cell infusion in 2009, additional insights have emerged from this and related work, including the discovery in animals that iron-infused cardiac stem cells can be guided with a magnet to damaged areas of the heart, dramatically increasing their retention and healing potential.

Another finding to emerge from Marbns cardiac stem cell lab may have implications for many peoples health: Stem cells exposed to high doses of supplemental antioxidants can develop genetic abnormalities that predispose them to cancer formation.

Click here to watch a CBS Evening News story about the clinical trials results.

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Cardiac Stem Cell Research - Cedars-Sinai

Heart attacks and congestive heart failure remain among the Nation's most prominent health challenges despite many breakthroughs in cardiovascular medicine. In fact, despite successful approaches to prevent or limit cardiovascular disease, the restoration of function to the damaged heart remains a formidable challenge. Recent research is providing early evidence that adult and embryonic stem cells may be able to replace damaged heart muscle cells and establish new blood vessels to supply them. Discussed here are some of the recent discoveries that feature stem cell replacement and muscle regeneration strategies for repairing the damaged heart.

For those suffering from common, but deadly, heart diseases, stem cell biology represents a new medical frontier. Researchers are working toward using stem cells to replace damaged heart cells and literally restore cardiac function.

Today in the United States, congestive heart failurethe ineffective pumping of the heart caused by the loss or dysfunction of heart muscle cellsafflicts 4.8 million people, with 400,000 new cases each year. One of the major contributors to the development of this condition is a heart attack, known medically as a myocardial infarction, which occurs in nearly 1.1 million Americans each year. It is easy to recognize that impairments of the heart and circulatory system represent a major cause of death and disability in the United States [5].

What leads to these devastating effects? The destruction of heart muscle cells, known as cardiomyocytes, can be the result of hypertension, chronic insufficiency in the blood supply to the heart muscle caused by coronary artery disease, or a heart attack, the sudden closing of a blood vessel supplying oxygen to the heart. Despite advances in surgical procedures, mechanical assistance devices, drug therapy, and organ transplantation, more than half of patients with congestive heart failure die within five years of initial diagnosis. Research has shown that therapies such as clot-busting medications can reestablish blood flow to the damaged regions of the heart and limit the death of cardiomyocytes. Researchers are now exploring ways to save additional lives by using replacement cells for dead or impaired cells so that the weakened heart muscle can regain its pumping power.

How might stem cells play a part in repairing the heart? To answer this question, researchers are building their knowledge base about how stem cells are directed to become specialized cells. One important type of cell that can be developed is the cardiomyocyte, the heart muscle cell that contracts to eject the blood out of the heart's main pumping chamber (the ventricle). Two other cell types are important to a properly functioning heart are the vascular endothelial cell, which forms the inner lining of new blood vessels, and the smooth muscle cell, which forms the wall of blood vessels. The heart has a large demand for blood flow, and these specialized cells are important for developing a new network of arteries to bring nutrients and oxygen to the cardiomyocytes after a heart has been damaged. The potential capability of both embryonic and adult stem cells to develop into these cells types in the damaged heart is now being explored as part of a strategy to restore heart function to people who have had heart attacks or have congestive heart failure. It is important that work with stem cells is not confused with recent reports that human cardiac myocytes may undergo cell division after myocardial infarction [1]. This work suggests that injured heart cells can shift from a quiescent state into active cell division. This is not different from the ability of a host of other cells in the body that begin to divide after injury. There is still no evidence that there are true stem cells in the heart which can proliferate and differentiate.

Researchers now know that under highly specific growth conditions in laboratory culture dishes, stem cells can be coaxed into developing as new cardiomyocytes and vascular endothelial cells. Scientists are interested in exploiting this ability to provide replacement tissue for the damaged heart. This approach has immense advantages over heart transplant, particularly in light of the paucity of donor hearts available to meet current transplantation needs.

What is the evidence that such an approach to restoring cardiac function might work? In the research laboratory, investigators often use a mouse or rat model of a heart attack to study new therapies (see Figure 9.1. Rodent Model of Myocardial Infarction). To create a heart attack in a mouse or rat, a ligature is placed around a major blood vessel serving the heart muscle, thereby depriving the cardiomyocytes of their oxygen and nutrient supplies. During the past year, researchers using such models have made several key discoveries that kindled interest in the application of adult stem cells to heart muscle repair in animal models of heart disease.

Figure 9.1. Rodent Model of Myocardial Infarction.

( 2001 Terese Winslow, Lydia Kibiuk)

Recently, Orlic and colleagues [9] reported on an experimental application of hematopoietic stem cells for the regeneration of the tissues in the heart. In this study, a heart attack was induced in mice by tying off a major blood vessel, the left main coronary artery. Through the identification of unique cellular surface markers, the investigators then isolated a select group of adult primitive bone marrow cells with a high capacity to develop into cells of multiple types. When injected into the damaged wall of the ventricle, these cells led to the formation of new cardiomyocytes, vascular endothelium, and smooth muscle cells, thus generating de novo myocardium, including coronary arteries, arterioles, and capillaries. The newly formed myocardium occupied 68 percent of the damaged portion of the ventricle nine days after the bone marrow cells were transplanted, in effect replacing the dead myocardium with living, functioning tissue. The researchers found that mice that received the transplanted cells survived in greater numbers than mice with heart attacks that did not receive the mouse stem cells. Follow-up experiments are now being conducted to extend the posttransplantation analysis time to determine the longer-range effects of such therapy [8]. The partial repair of the damaged heart muscle suggests that the transplanted mouse hematopoietic stem cells responded to signals in the environment near the injured myocardium. The cells migrated to the damaged region of the ventricle, where they multiplied and became "specialized" cells that appeared to be cardiomyocytes.

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9. Can Stem Cells Repair a Damaged Heart? [Stem Cell Information]

Adult Stem Cell Enhancer by Dr. Riordan, Chinese subtitle.
Consistently Increase of 50-100% Bone Marrow stem cells. Dr. Riordan Introduces Adult Stem cell Enhancer From RBC Life #39;s Stem-Kine with Dr. Clinton Howard an...

By: Adam Kee

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Adult Stem Cell Enhancer by Dr. Riordan, Chinese subtitle. - Video

Bone marrow is the spongy tissue inside some of your bones, such as your hip and thigh bones. It contains immature cells, called stem cells. The stem cells can develop into the red blood cells that carry oxygen through your body, the white blood cells that fight infections, and the platelets that help with blood clotting.

If you have a bone marrow disease, there are problems with the stem cells or how they develop. Leukemia is a cancer in which the bone marrow produces abnormal white blood cells. With aplastic anemia, the bone marrow doesn't make red blood cells. Other diseases, such as lymphoma, can spread into the bone marrow and affect the production of blood cells. Other causes of bone marrow disorders include your genetic makeup and environmental factors.

Symptoms of bone marrow diseases vary. Treatments depend on the disorder and how severe it is. They might involve medicines, blood transfusions or a bone marrow transplant.

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Bone Marrow Diseases: MedlinePlus - U.S. National Library of Medicine

Hematopoietic stem cell transplantation (HSCT) is the transplantation of multipotent hematopoietic stem cells, usually derived from bone marrow, peripheral blood, or umbilical cord blood. It is a medical procedure in the fields of hematology and oncology, most often performed for patients with certain cancers of the blood or bone marrow, such as multiple myeloma or leukemia. In these cases, the recipient's immune system is usually destroyed with radiation or chemotherapy before the transplantation. Infection and graft-versus-host disease is a major complication of allogenic HSCT.

Hematopoietic stem cell transplantation remains a dangerous procedure with many possible complications; it is reserved for patients with life-threatening diseases. As the survival of the procedure increases, its use has expanded beyond cancer, such as autoimmune diseases.[1][2]

Many recipients of HSCTs are multiple myeloma[3] or leukemia patients[4] who would not benefit from prolonged treatment with, or are already resistant to, chemotherapy. Candidates for HSCTs include pediatric cases where the patient has an inborn defect such as severe combined immunodeficiency or congenital neutropenia with defective stem cells, and also children or adults with aplastic anemia[5] who have lost their stem cells after birth. Other conditions[6] treated with stem cell transplants include sickle-cell disease, myelodysplastic syndrome, neuroblastoma, lymphoma, Ewing's sarcoma, desmoplastic small round cell tumor, chronic granulomatous disease and Hodgkin's disease. More recently non-myeloablative, or so-called "mini transplant," procedures have been developed that require smaller doses of preparative chemo and radiation. This has allowed HSCT to be conducted in the elderly and other patients who would otherwise be considered too weak to withstand a conventional treatment regimen.

A total of 50,417 first hematopoietic stem cell transplants were reported as taking place worldwide in 2006, according to a global survey of 1327 centers in 71 countries conducted by the Worldwide Network for Blood and Marrow Transplantation. Of these, 28,901 (57%) were autologous and 21,516 (43%) were allogenetic (11,928 from family donors and 9,588 from unrelated donors). The main indications for transplant were lymphoproliferative disorders (54.5%) and leukemias (33.8%), and the majority took place in either Europe (48%) or the Americas (36%).[7] In 2009, according to the world marrow donor association, stem cell products provided for unrelated transplantation worldwide had increased to 15,399 (3,445 bone marrow donations, 8,162 peripheral blood stem cell donations, and 3,792 cord blood units).[8]

Autologous HSCT requires the extraction (apheresis) of haematopoietic stem cells (HSC) from the patient and storage of the harvested cells in a freezer. The patient is then treated with high-dose chemotherapy with or without radiotherapy with the intention of eradicating the patient's malignant cell population at the cost of partial or complete bone marrow ablation (destruction of patient's bone marrow function to grow new blood cells). The patient's own stored stem cells are then transfused into his/her bloodstream, where they replace destroyed tissue and resume the patient's normal blood cell production. Autologous transplants have the advantage of lower risk of infection during the immune-compromised portion of the treatment since the recovery of immune function is rapid. Also, the incidence of patients experiencing rejection (graft-versus-host disease) is very rare due to the donor and recipient being the same individual. These advantages have established autologous HSCT as one of the standard second-line treatments for such diseases as lymphoma.[9] However, for others such as Acute Myeloid Leukemia, the reduced mortality of the autogenous relative to allogeneic HSCT may be outweighed by an increased likelihood of cancer relapse and related mortality, and therefore the allogeneic treatment may be preferred for those conditions.[10] Researchers have conducted small studies using non-myeloablative hematopoietic stem cell transplantation as a possible treatment for type I (insulin dependent) diabetes in children and adults. Results have been promising; however, as of 2009[update] it was premature to speculate whether these experiments will lead to effective treatments for diabetes.[11]

Allogeneic HSCT involves two people: the (healthy) donor and the (patient) recipient. Allogeneic HSC donors must have a tissue (HLA) type that matches the recipient. Matching is performed on the basis of variability at three or more loci of the HLA gene, and a perfect match at these loci is preferred. Even if there is a good match at these critical alleles, the recipient will require immunosuppressive medications to mitigate graft-versus-host disease. Allogeneic transplant donors may be related (usually a closely HLA matched sibling), syngeneic (a monozygotic or 'identical' twin of the patient - necessarily extremely rare since few patients have an identical twin, but offering a source of perfectly HLA matched stem cells) or unrelated (donor who is not related and found to have very close degree of HLA matching). Unrelated donors may be found through a registry of bone marrow donors such as the National Marrow Donor Program. People who would like to be tested for a specific family member or friend without joining any of the bone marrow registry data banks may contact a private HLA testing laboratory and be tested with a mouth swab to see if they are a potential match.[12] A "savior sibling" may be intentionally selected by preimplantation genetic diagnosis in order to match a child both regarding HLA type and being free of any obvious inheritable disorder. Allogeneic transplants are also performed using umbilical cord blood as the source of stem cells. In general, by transfusing healthy stem cells to the recipient's bloodstream to reform a healthy immune system, allogeneic HSCTs appear to improve chances for cure or long-term remission once the immediate transplant-related complications are resolved.[13][14][15]

A compatible donor is found by doing additional HLA-testing from the blood of potential donors. The HLA genes fall in two categories (Type I and Type II). In general, mismatches of the Type-I genes (i.e. HLA-A, HLA-B, or HLA-C) increase the risk of graft rejection. A mismatch of an HLA Type II gene (i.e. HLA-DR, or HLA-DQB1) increases the risk of graft-versus-host disease. In addition a genetic mismatch as small as a single DNA base pair is significant so perfect matches require knowledge of the exact DNA sequence of these genes for both donor and recipient. Leading transplant centers currently perform testing for all five of these HLA genes before declaring that a donor and recipient are HLA-identical.

Race and ethnicity are known to play a major role in donor recruitment drives, as members of the same ethnic group are more likely to have matching genes, including the genes for HLA.[1]

To limit the risks of transplanted stem cell rejection or of severe graft-versus-host disease in allogeneic HSCT, the donor should preferably have the same human leukocyte antigens (HLA) as the recipient. About 25 to 30 percent of allogeneic HSCT recipients have an HLA-identical sibling. Even so-called "perfect matches" may have mismatched minor alleles that contribute to graft-versus-host disease.

In the case of a bone marrow transplant, the HSC are removed from a large bone of the donor, typically the pelvis, through a large needle that reaches the center of the bone. The technique is referred to as a bone marrow harvest and is performed under general anesthesia.

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Hematopoietic stem cell transplantation - Wikipedia, the free ...

What are bone marrow and hematopoietic stem cells?

Bone marrow is the soft, sponge-like material found inside bones. It contains immature cells known as hematopoietic or blood-forming stem cells. (Hematopoietic stem cells are different from embryonic stem cells. Embryonic stem cells can develop into every type of cell in the body.) Hematopoietic stem cells divide to form more blood-forming stem cells, or they mature into one of three types of blood cells: white blood cells, which fight infection; red blood cells, which carry oxygen; and platelets, which help the blood to clot. Most hematopoietic stem cells are found in the bone marrow, but some cells, called peripheral blood stem cells (PBSCs), are found in the bloodstream. Blood in the umbilical cord also contains hematopoietic stem cells. Cells from any of these sources can be used in transplants.

What are bone marrow transplantation and peripheral blood stem cell transplantation?

Bone marrow transplantation (BMT) and peripheral blood stem cell transplantation (PBSCT) are procedures that restore stem cells that have been destroyed by high doses of chemotherapy and/or radiation therapy. There are three types of transplants:

Why are BMT and PBSCT used in cancer treatment?

One reason BMT and PBSCT are used in cancer treatment is to make it possible for patients to receive very high doses of chemotherapy and/or radiation therapy. To understand more about why BMT and PBSCT are used, it is helpful to understand how chemotherapy and radiation therapy work.

Chemotherapy and radiation therapy generally affect cells that divide rapidly. They are used to treat cancer because cancer cells divide more often than most healthy cells. However, because bone marrow cells also divide frequently, high-dose treatments can severely damage or destroy the patients bone marrow. Without healthy bone marrow, the patient is no longer able to make the blood cells needed to carry oxygen, fight infection, and prevent bleeding. BMT and PBSCT replace stem cells destroyed by treatment. The healthy, transplanted stem cells can restore the bone marrows ability to produce the blood cells the patient needs.

In some types of leukemia, the graft-versus-tumor (GVT) effect that occurs after allogeneic BMT and PBSCT is crucial to the effectiveness of the treatment. GVT occurs when white blood cells from the donor (the graft) identify the cancer cells that remain in the patients body after the chemotherapy and/or radiation therapy (the tumor) as foreign and attack them. (A potential complication of allogeneic transplants called graft-versus-host disease is discussed in Questions 5 and 14.)

What types of cancer are treated with BMT and PBSCT?

BMT and PBSCT are most commonly used in the treatment of leukemia and lymphoma. They are most effective when the leukemia or lymphoma is in remission (the signs and symptoms of cancer have disappeared). BMT and PBSCT are also used to treat other cancers such as neuroblastoma (cancer that arises in immature nerve cells and affects mostly infants and children) and multiple myeloma. Researchers are evaluating BMT and PBSCT in clinical trials (research studies) for the treatment of various types of cancer.

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This article is about the medical aspects of bone marrow in humans. For use of animal bone marrow in cuisine, see Bone marrow (food).

Bone marrow is the flexible tissue in the interior of bones. In humans, red blood cells are produced in the heads of long bones in a process known as hematopoiesis. On average, bone marrow constitutes 4% of the total body mass of humans; in an adult weighing 65 kilograms (143lb), bone marrow typically accounts for approximately 2.6 kilograms (5.7lb). The hematopoietic component of bone marrow produces approximately 500 billion blood cells per day, which use the bone marrow vasculature as a conduit to the body's systemic circulation.[1] Bone marrow is also a key component of the lymphatic system, producing the lymphocytes that support the body's immune system.[2]

Bone marrow transplants can be conducted to treat severe diseases of the bone marrow, including certain forms of cancer. Additionally, bone marrow stem cells have been successfully transformed into functional neural cells,[3] and can also potentially be used to treat illnesses such as inflammatory bowel disease[4] and, in some cases, HIV.[5][6]

The two types of bone marrow are medulla ossium rubra (red marrow), which consists mainly of hematopoietic tissue, and medulla ossium flava (yellow marrow), which is mainly made up of fat cells. Red blood cells, platelets and most white blood cells arise in red marrow. Both types of bone marrow contain numerous blood vessels and capillaries. At birth, all bone marrow is red. With age, more and more of it is converted to the yellow type; only around half of adult bone marrow is red. Red marrow is found mainly in the flat bones, such as the pelvis, sternum, cranium, ribs, vertebrae and scapulae, and in the cancellous ("spongy") material at the epiphyseal ends of long bones such as the femur and humerus. Yellow marrow is found in the medullary cavity, the hollow interior of the middle portion of long bones. In cases of severe blood loss, the body can convert yellow marrow back to red marrow to increase blood cell production.

The stroma of the bone marrow is all tissue not directly involved in the marrow's primary function of hematopoiesis. Yellow bone marrow makes up the majority of bone marrow stroma, in addition to smaller concentrations of stromal cells located in the red bone marrow. Though not as active as parenchymal red marrow, stroma is indirectly involved in hematopoiesis, since it provides the hematopoietic microenvironment that facilitates hematopoiesis by the parenchymal cells. For instance, they generate colony stimulating factors, which have a significant effect on hematopoiesis. Cell types that constitute the bone marrow stroma include:

The blood vessels of the bone marrow constitute a barrier, inhibiting immature blood cells from leaving the marrow. Only mature blood cells contain the membrane proteins required to attach to and pass the blood vessel endothelium. Hematopoietic stem cells may also cross the bone marrow barrier, and may thus be harvested from blood.

The bone marrow stroma contains mesenchymal stem cells (MSCs),[7] also known as marrow stromal cells. These are multipotent stem cells that can differentiate into a variety of cell types. MSCs have been shown to differentiate, in vitro or in vivo, into osteoblasts, chondrocytes, myocytes, adipocytes and beta-pancreatic islets cells. MSCs can also transdifferentiate into neuronal cells.[3]

In addition, the bone marrow contains hematopoietic stem cells, which give rise to the three classes of blood cells that are found in the circulation: white blood cells (leukocytes), red blood cells (erythrocytes), and platelets (thrombocytes).[7]

Biological compartmentalization is evident within the bone marrow, in that certain cell types tend to aggregate in specific areas. For instance, erythrocytes, macrophages, and their precursors tend to gather around blood vessels, while granulocytes gather at the borders of the bone marrow.

The red bone marrow is a key element of the lymphatic system, being one of the primary lymphoid organs that generate lymphocytes from immature hematopoietic progenitor cells.[2] The bone marrow and thymus constitute the primary lymphoid tissues involved in the production and early selection of lymphocytes. Furthermore, bone marrow performs a valve-like function to prevent the backflow of lymphatic fluid in the lymphatic system.

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Bone marrow - Wikipedia, the free encyclopedia

By Jeanette Jacknin M.D.

Dr Jacknin will be speaking about Cosmaceuticals at the upcoming 17th World Congress on Anti-Aging and Regenerative Medicine in Orlando, Florida, April 23-25, 2009.

Stem cells have recently become a huge buzzword in the skincare world. But what does this really mean? Skincare specialists are not using embryonic stem cells; it is impossible to incorporate live materials into a skincare product. Instead, companies are creating products with specialized peptides and enzymes or plant stem cells which, when applied topically on the surface, help protect the human skin stem cells from damage and deterioration or stimulate the skin's own stem cells. National Stem Cell was one of the few companies who actually incorporated into their skin care an enzyme secreted from human embryonic stem cells, but they are in the process of switching over to use non-embryonic stem cells from which to take the beneficial enzyme.

Stem cells have the remarkable potential to develop into many different cell types in the body. When a stem cell divides, it can remain a stem cell or become another type of cell with a more specialized function, such as a skin cell. There are two types of stem cells, embryonic and adult.

Embryonic stem cells are exogenous in that they are harvested from outside sources, namely, fertilized human eggs. Once harvested, these pluripotent stem cells are grown in cell cultures and manipulated to generate specific cell types so they can be used to treat injury or disease.

Unlike embryonic stem cells, adult or multipotent stem cells are endogenous. They are present within our bodies and serve to maintain and repair the tissues in which they are found. Adult stem cells are found in many organs and tissues, including the skin. In fact, human skin is the largest repository of adult stem cells in the body. Skin stem cells reside in the basal layer of the epidermis where they remain dormant until they are activated by tissue injury or disease. 1

There is controversy surrounding the use of stem cells, as some experts say that any product that claims to affect the growth of stem cells or the replication process is potentially dangerous, as it may lead to out-of-control replication or mutation. Others object to using embryonic stem cells from an ethical point of view. Some researchers believe that the use of stem cell technology for a topical, anti-aging cosmetic trivializes other, more important medical research in this field.

The skin stem cells are found near hair follicles and sweat glands and lie dormant until they "receive" signals from the body to begin the repair mode. In skincare, the use of topical products stimulates the stem cell to split into two types of cells: a new, similar stem cell and a "daughter" cell, which is able to create almost every kind of new cell in a specialized system. This means that the stem cell can receive the message to create proteins, carbohydrates and lipids to help repair fine lines, wrinkles and restore and maintain firmness and elasticity.1

First to the market in Britain in April 2007 and the U.S. was ReVive's Peau Magnifique, priced at a staggering 1,050. Manufacturers claim it uses an enzyme called telomerase to "convert resting adult stem cells to newly-minted skin cells' and 'effectively resets your skin's "ageing clock" by a minimum of five years'. The product claims long-term use 'will result in a generation of new skin cells, firmer skin with a 45 per cent reduction in wrinkles and increased long-term skin clarity'. Peau Magnifique is the latest in a line of products developed by Dr Gregory Bays Brown, a former plastic surgeon.

In the course of his research into healing burns victims, Dr Brown discovered a substance called Epidermal Growth Factor (EGF) that is released in the body when there is an injury, and, when applied to burns or wounds, dramatically accelerates the healing process. He believed the same molecule could be used to regenerate ageing skin and went on to develop ReVive, a skincare range based around it. 2

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Stem cells in skin care...What does it really mean? | Worldhealth ...

Stem cells are undifferentiated biological cells, that can differentiate into specialized cells and can divide (through mitosis) to produce more stem cells. They are found in multicellular organisms. In mammals, there are two broad types of stem cells: embryonic stem cells, which are isolated from the inner cell mass of blastocysts, and adult stem cells, which are found in various tissues. In adult organisms, stem cells and progenitor cells act as a repair system for the body, replenishing adult tissues. In a developing embryo, stem cells can differentiate into all the specialized cellsectoderm, endoderm and mesoderm (see induced pluripotent stem cells)but also maintain the normal turnover of regenerative organs, such as blood, skin, or intestinal tissues.

There are three accessible sources of autologous adult stem cells in humans:

Stem cells can also be taken from umbilical cord blood just after birth. Of all stem cell types, autologous harvesting involves the least risk. By definition, autologous cells are obtained from one's own body, just as one may bank his or her own blood for elective surgical procedures.

Highly plastic adult stem cells are routinely used in medical therapies, for example in bone marrow transplantation. Stem cells can now be artificially grown and transformed (differentiated) into specialized cell types with characteristics consistent with cells of various tissues such as muscles or nerves through cell culture. Embryonic cell lines and autologous embryonic stem cells generated through therapeutic cloning have also been proposed as promising candidates for future therapies.[1] Research into stem cells grew out of findings by Ernest A. McCulloch and James E. Till at the University of Toronto in the 1960s.[2][3]

The classical definition of a stem cell requires that it possess two properties:

Two mechanisms exist to ensure that a stem cell population is maintained:

Potency specifies the differentiation potential (the potential to differentiate into different cell types) of the stem cell.[4]

The practical definition of a stem cell is the functional definitiona cell that has the potential to regenerate tissue over a lifetime. For example, the defining test for a bone marrow or hematopoietic stem cell (HSC) is the ability to transplant one cell and save an individual without HSCs. In this case, a stem cell must be able to produce new blood cells and immune cells over a long term, demonstrating potency. It should also be possible to isolate stem cells from the transplanted individual, which can themselves be transplanted into another individual without HSCs, demonstrating that the stem cell was able to self-renew.

Properties of stem cells can be illustrated in vitro, using methods such as clonogenic assays, in which single cells are assessed for their ability to differentiate and self-renew.[7][8] Stem cells can also be isolated by their possession of a distinctive set of cell surface markers. However, in vitro culture conditions can alter the behavior of cells, making it unclear whether the cells will behave in a similar manner in vivo. There is considerable debate as to whether some proposed adult cell populations are truly stem cells.

Embryonic stem (ES) cell lines are cultures of cells derived from the epiblast tissue of the inner cell mass (ICM) of a blastocyst or earlier morula stage embryos.[9] A blastocyst is an early stage embryoapproximately four to five days old in humans and consisting of 50150 cells. ES cells are pluripotent and give rise during development to all derivatives of the three primary germ layers: ectoderm, endoderm and mesoderm. In other words, they can develop into each of the more than 200 cell types of the adult body when given sufficient and necessary stimulation for a specific cell type. They do not contribute to the extra-embryonic membranes or the placenta. The endoderm is composed of the entire gut tube and the lungs, the ectoderm gives rise to the nervous system and skin, and the mesoderm gives rise to muscle, bone, bloodin essence, everything else that connects the endoderm to the ectoderm.

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Stem cell - Wikipedia, the free encyclopedia

home stem cell research all about stem cells what are stem cells?

Stem cells are a class of undifferentiated cells that are able to differentiate into specialized cell types. Commonly, stem cells come from two main sources:

Both types are generally characterized by their potency, or potential to differentiate into different cell types (such as skin, muscle, bone, etc.).

Adult or somatic stem cells exist throughout the body after embryonic development and are found inside of different types of tissue. These stem cells have been found in tissues such as the brain, bone marrow, blood, blood vessels, skeletal muscles, skin, and the liver. They remain in a quiescent or non-dividing state for years until activated by disease or tissue injury.

Adult stem cells can divide or self-renew indefinitely, enabling them to generate a range of cell types from the originating organ or even regenerate the entire original organ. It is generally thought that adult stem cells are limited in their ability to differentiate based on their tissue of origin, but there is some evidence to suggest that they can differentiate to become other cell types.

Embryonic stem cells are derived from a four- or five-day-old human embryo that is in the blastocyst phase of development. The embryos are usually extras that have been created in IVF (in vitro fertilization) clinics where several eggs are fertilized in a test tube, but only one is implanted into a woman.

Sexual reproduction begins when a male's sperm fertilizes a female's ovum (egg) to form a single cell called a zygote. The single zygote cell then begins a series of divisions, forming 2, 4, 8, 16 cells, etc. After four to six days - before implantation in the uterus - this mass of cells is called a blastocyst. The blastocyst consists of an inner cell mass (embryoblast) and an outer cell mass (trophoblast). The outer cell mass becomes part of the placenta, and the inner cell mass is the group of cells that will differentiate to become all the structures of an adult organism. This latter mass is the source of embryonic stem cells - totipotent cells (cells with total potential to develop into any cell in the body).

In a normal pregnancy, the blastocyst stage continues until implantation of the embryo in the uterus, at which point the embryo is referred to as a fetus. This usually occurs by the end of the 10th week of gestation after all major organs of the body have been created.

However, when extracting embryonic stem cells, the blastocyst stage signals when to isolate stem cells by placing the "inner cell mass" of the blastocyst into a culture dish containing a nutrient-rich broth. Lacking the necessary stimulation to differentiate, they begin to divide and replicate while maintaining their ability to become any cell type in the human body. Eventually, these undifferentiated cells can be stimulated to create specialized cells.

Stem cells are either extracted from adult tissue or from a dividing zygote in a culture dish. Once extracted, scientists place the cells in a controlled culture that prohibits them from further specializing or differentiating but usually allows them to divide and replicate. The process of growing large numbers of embryonic stem cells has been easier than growing large numbers of adult stem cells, but progress is being made for both cell types.

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The term stem cell by itself can be misleading. There are many different types of stem cells, each with very different potential to treat disease. The so-called adult stem cells come from any organ, from the fetus through the adult. These are also called tissue stem cells. The so-called pluripotent cells, which have the ability to form all cells in the body, can be either embryonic or induced pluripotent stem (iPS) cells.

All stem cells, whether they are tissue stem cells or pluripotent cells, have the ability to divide and create an identical copy of themselves. This process is called self-renewal. The cells can also divide to form cells that go on to develop into mature tissue types such as liver, lungs, brain, or skin.

Embryonic stem cells exist only at the earliest stages of embryonic development and go on to form all the cells of the adult body. In humans, these cells no longer exist after about five days of development.

When removed and grown in a lab dish these stem cells can continue dividing indefinitely, retaining the ability to form the more than 200 adult cell types. Because the cells have the potential to form so many different adult tissues they are also called pluripotent ("pluri" = many, "potent" = potentials) stem cells.

James Thomson, a professor of Anatomy at the University of Wisconsin, isolated the first human embryonic stem cells in 1998. He now shares a joint appointment at the University of California, Santa Barbara.

Irv Weissman talks about the difference between adult and embryonic stem cells (3:29)

Pluripotent means many (pluri) potentials (potent). In other words, these cells have the potential of taking on many fates in the body, including all of the more than 200 different cell types. Embryonic stem cells are pluripotent, as are iPS cells that are reprogrammed from adult tissues. When scientists talk about pluripotent stem cells they mostly mean either embryonic or iPS cells.

What people commonly call adult stem cells are more accurately called tissue-specific stem cells. These are specialized cells found in tissues of adults, children and fetuses. They are thought to exist in most of the bodys tissues such as the blood, brain, liver, intestine or skin. These cells are committed to becoming a cell from their tissue of origin, but they still have the broad ability to become any one of these cells. Stem cells of the bone marrow, for example, can give rise to any of the red or white cells of the blood system. Stem cells in the brain can form all the neurons and support cells of the brain, but cant form non-brain tissues. Unlike embryonic stem cells, researchers have not been able to grow adult stem cells indefinitely in the lab.

In recent years, scientists have found stem cells in the placenta and in the umbilical cord of newborn infants. Although these cells come from a newborn they are like adult stem cells in that they are already committed to becoming a particular type of cell and cant go on to form all tissues of the body. The cord blood cells that some people bank after the birth of a child are a form of adult blood-forming stem cells.

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Stem Cell Definitions | California's Stem Cell Agency

In November 2007 scientists announced they had developed a new way to cause mature human cells to resemble pluripotent stem cells - similar in many ways to human embryonic stem cells. By simply altering the expression of just four genes using genetic modification, the mature cells were 'induced' to become more primitive, stem cells and were referred to as 'induced' pluripotent stem (iPS) cells.

Initially iPS cells were generated using viruses to change gene expression, however since the initial discovery, technologies for reprogramming cells are moving very quickly and researchers are now investigating the use of new methods that do not use viruses which can cause permanent and potentially harmful changes in the cells. If they are able to be made safely, and on a large scale, iPS cells could possibly be used to provide a source of cells to replace cells damaged following illness or disease. It may even be possible to make stem cells for therapy from a patient's own cells and thereby avoid the use of anti-rejection medications.

However, right now scientists are using this method to create disease specific cells for research by taking a cells - maybe from a skin biopsy - from a patient with a genetic disorder, such as Huntingtons disease, and then using the iPS cells to study the disease in the laboratory. Scientist hope that such an approach will help them understand the development and progression of certain diseases, and assist in the development and testing of new drugs to treat disease.

While the discovery of iPS cells was a very important development, more research needs to be done to discover if they will offer the same research value as embryonic stem cells and if they will be as useful for therapy.

To learn more about iPS cells watch What are induced pluripotent stem cells? in our video library.

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What are induced pluripotent stem cells or iPS cells? - Stem Cells ...

Induced pluripotent stem cells,[1] 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 specific genes.

Induced pluripotent stem cells are similar to natural pluripotent stem cells, such as embryonic stem (ES) cells, in many aspects, such as the expression of certain stem cell genes and proteins, chromatin methylation patterns, doubling time, embryoid body formation, teratoma formation, viable chimera formation, and potency and differentiability, but the full extent of their relation to natural pluripotent stem cells is still being assessed.[2] Induced pluripotent cells have been made from adult stomach, liver, skin cells, blood cells, prostate cells and urinary tract cells.[3]

iPSCs were first produced in 2006 from mouse cells and in 2007 from human cells in a series of experiments by Shinya Yamanaka's team at Kyoto University, Japan, and by James Thomson's team at the University of Wisconsin-Madison. For her iPSC research, Dr. Nancy Bachman, of Oneonta, NY, was awarded the Wolf Prize in Medicine in 2012 (along with John B. Gurdon).[4][5][6] For his iPSC discovery (and for deriving the first human embryonic stem cell), James Thomson received the 2011 Albany Medical Center Prize for Biomedical Research and the 2011 King Faisal International Prize, which he shared with Yamanaka. In October 2012, Yamanaka and fellow stem cell researcher John Gurdon were awarded the Nobel Prize in Physiology or Medicine "for the discovery that mature cells can be reprogrammed to become pluripotent."[7]

iPSCs are an important advance in stem cell research, as they may allow researchers to obtain pluripotent stem cells, which are important in research and potentially have therapeutic uses, without the controversial use of embryos. Because iPSCs are developed from a patient's own somatic cells, it was believed that treatment of iPSCs would avoid any immunogenic responses; however, Zhao et al. have challenged this assumption.[8]

Depending on the methods used, reprogramming of adult cells to obtain iPSCs may pose significant risks that could limit their use in humans. For example, if viruses are used to genomically alter the cells, the expression of cancer-causing genes "oncogenes" may potentially be triggered. In February 2008, scientists announced the discovery of a technique that could remove oncogenes after the induction of pluripotency, thereby increasing the potential use of iPS cells in human diseases.[9] In April 2009, it was demonstrated that generation of iPS cells is possible without any genetic alteration of the adult cell: a repeated treatment of the cells with certain proteins channeled into the cells via poly-arginine anchors was sufficient to induce pluripotency.[10] The acronym given for those iPSCs is piPSCs (protein-induced pluripotent stem cells).

Dedifferentiation to totipotency or pluripotency: an overview of methods. Various methods exist to revert adult somatic cells to pluripotency or totipotency. In the case of totipotency, reprogramming is mediated through a mature metaphase II oocyte as in somatic cell nuclear transfer (Wilmut et al., 1997). Recent work has demonstrated the feasibility of enucleated zygotes or early blastomeres chemically arrested during mitosis, such that nuclear envelope break down occurs, to support reprogramming to totipotency in a process called chromosome transfer (Egli and Eggan, 2010). Direct reprogramming methods support reversion to pluripotency; though, vehicles and biotypes vary considerably in efficiencies (Takahashi and Yamanaka, 2006). Viral-mediated transduction robustly supports dedifferentiation to pluripotency through retroviral or DNA-viral routes but carries the onus of insertional inactivation. Additionally, epigenetic reprogramming by enforced expression of OSKM through DNA routes exists such as plasmid DNA, minicircles, transposons, episomes and DNA mulicistronic construct targeting by homologous recombination has also been demonstrated; however, these methods suffer from the burden to potentially alter the recipient genome by gene insertion (Ho et al., 2010). While protein-mediated transduction supports reprogramming adult cells to pluripotency, the method is cumbersome and requires recombinant protein expression and purification expertise, and reprograms albeit at very low frequencies (Kim et al., 2009). A major obstacle of using RNA for reprogramming is its lability and that single-stranded RNA biotypes trigger innate antiviral defense pathways such as interferon and NF-B-dependent pathways. In vitro transcribed RNA, containing stabilizing modifications such as 5-methylguanosine capping or substituted ribonucleobases, e.g. pseudouracil, is 35-fold more efficient than viral transduction and has the additional benefit of not altering the somatic genome (Warren et al., 2010). An overarching goal of reprogramming methods is to replace genes with small molecules to assist in reprogramming. No cocktail has been identified to completely reprogram adult cells to totipotency or pluripotency, but many examples exist that improve the overall efficiency of the process and can supplant one or more genes by direct reprogramming routes (Feng et al., 2009; Zhu et al., 2010).

iPS cells are typically derived by transfection of certain stem cell-associated genes into non-pluripotent cells, such as adult fibroblasts, although this technique is becoming less popular since it is known to be prone to inducing cancer formation. Transfection is typically achieved through viral vectors, such as retroviruses. Transfected genes include the master transcriptional regulators Oct-3/4 (Pou5f1) and Sox2, although it is suggested that other genes enhance the efficiency of induction. After 34 weeks, small numbers of transfected cells begin to become morphologically and biochemically similar to pluripotent stem cells, and are typically isolated through morphological selection, doubling time, or through a reporter gene and antibiotic selection.

Induced pluripotent stem cells were first generated by Shinya Yamanaka's team at Kyoto University, Japan in 2006. Yamanaka used genes that had been identified as particularly important in embryonic stem cells (ESCs), and used retroviruses to transduce mouse fibroblasts with a selection of those genes. Eventually, four key pluripotency genes essential for the production of pluripotent stem cells were isolated; Oct-3/4, SOX2, c-Myc, and Klf4. Cells were isolated by antibiotic selection of Fbx15+ cells. However, this iPS cell line showed DNA methylation errors compared to original patterns in ESC lines and failed to produce viable chimeras if injected into developing embryos.

In June 2007, the same group published a breakthrough study along with two other independent research groups from Harvard, MIT, and the University of California, Los Angeles, showing successful reprogramming of mouse fibroblasts into iPS cells and even producing viable chimera. These cell lines were also derived from mouse fibroblasts by retroviral mediated reactivation of the same four endogenous pluripotent factors, but the researchers now selected a different marker for detection. Instead of Fbx15, they used Nanog which is an important gene in ESCs. DNA methylation patterns and production of viable chimeras (and thereby contributing to subsequent germ-line production) indicated that Nanog is a major determinant of cellular pluripotency.[11][12][13][14][15]

Unfortunately, two of the four genes used (namely, c-Myc and KLF4) are oncogenic, and 20% of the chimeric mice developed cancer. In a later study, Yamanaka reported that one can create iPSCs even without c-Myc. The process takes longer and is not as efficient, but the resulting chimeras didn't develop cancer.[16]

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Induced pluripotent stem cell - Wikipedia, the free encyclopedia

The Journal of Stem cells and Regenerative Medicine (JSRM) is a fully free access exclusive Online Journal covering areas of Basic Research, Translational work and Clinical studies in the specialty of Stem Cells and Regenerative Medicine including allied specialities such as Biomaterials and Nano technology relevant to the core subject. This has also been endorsed by the German Society for Stem Cell Research(GSZ).

The JSRM issues are published regularly and articles pertaining to Stem cells and Regenerative Medicine as well as related fields of research are considered for publication

This Online Journal conceived and run by Clinicians and Scientists, originally started for the student community with reputed members in the advisory/editorial boards, has now been accepted to be the official organ of GSZ is reaching millions of Researchers, Cliniciansand Students all over the world, as it is a FREE Journal

Current activities of JSRM

1. Journal issues: will be published online and to subscribers (FREE) extracts will be sent by email 2. Weekly updates on happenings in the Stem Cell World with email updates to subscribers.

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Stem Cell Therapy helps dog with DJD and ruptured ACL - Video