Induced pluripotent stem-cell therapy – Wikipedia
By LizaAVILA
In 2006, Shinya Yamanaka of Kyoto University in Japan was the first to disprove the previous notion that reversible cell differentiation of mammals was impossible. He reprogrammed a fully differentiated mouse cell into a pluripotent stem cell by introducing four genes, Oct-4, SOX2, KLF4, and Myc, into the mouse fibroblast through gene-carrying viruses. With this method, he and his coworkers created induced pluripotent stem cells (iPS cells), the key component in this experiment.[1] Scientists have been able to conduct experiments that show the ability of iPS cells to treat and even cure diseases. In this experiment, tests were run on mice with inherited sickle-cell anemia. Skin cells were turned into cells containing genes that transformed the cells into iPS cells. These replaced the diseased sickled cells, curing the test mice. The reprogramming of the pluripotent stem cells in mice was successfully duplicated with human pluripotent stem cells within about a year of the experiment on the mice.[citation needed]
Sickle-cell anemia is a disease in which the body produces abnormally shaped red blood cells. Red blood cells are flexible and round, moving easily through the blood vessels. Infected cells are shaped like a crescent or sickle (the namesake of the disease). As a result of this disorder the hemoglobin protein in red blood cells is faulty. Normal hemoglobin bonds to oxygen, then releases it into cells that need it. The blood cell retains its original form and is cycled back to the lungs and re-oxygenated.
Sickle cell hemoglobin, however, after giving up oxygen, cling together and make the red blood cell stiff. The sickle shape also makes it difficult for the red blood cell to navigate arteries and causes blockages.[2] This can cause intense pain and organ damage. The sickled red blood cells are fragile and prone to rupture. When the number of red blood cells decreases from rupture (hemolysis), anemia is the result. Sickle cells die in 1020 days as opposed to the traditional 120-day lifespan of a normal red blood cell.
Sickle cell anemia is inherited as an autosomal (meaning that the gene is not linked to a sex chromosome) recessive condition.[2] This means that the gene can be passed on from a carrier to his or her children. In order for sickle cell anemia to affect a person, the gene must be inherited from both the mother and the father, so that the child has two recessive sickle cell genes (a homozygous inheritance). People who inherit one sickle cell gene from one parent and one normal gene from the other parent, i.e. heterozygous patients, have a condition called sickle cell trait. Their bodies make both sickle hemoglobin and normal hemoglobin. They may pass the trait on to their children.
The effects of sickle-cell anemia vary from person to person. People who have the disease suffer from varying degrees of chronic pain and fatigue. With proper care and treatment, the quality of health of most patients will improve. Doctors have learned a great deal about sickle cell anemia since its discovery in 1979. They know its causes, its effects on the body, and possible treatments for complications. Sickle cell anemia has no widely available cure. A bone marrow transplant is the only treatment method currently recognized to be able to cure the disease, though it does not work for every patient. Finding a donor is difficult and the procedure could potentially do more harm than good. Treatments for sickle cell anemia are generally aimed at avoiding crises, relieving symptoms, and preventing complications. Such treatments may include medications, blood transfusions, and supplemental oxygen.
During the first step of the experiment, skin cells (also known as fibroblasts) were collected from infected test mice and put in a culture. The fibroblasts were reprogrammed by infecting them with retroviruses that contained genes common to embryonic stem cells. These genes were the same four used by Yamanaka (Oct-4, SOX2, KLF4, and Myc) in his earlier study. The investigators were trying to produce cells with the potential to differentiate into any type of cell needed (i.e. pluripotent stem cells). As the experiment continued, the fibroblasts multiplied into identical copies of iPS cells. The cells were then treated to form the mutation needed to reverse the anemia in the mice. This was accomplished by restructuring the DNA containing the defective globin gene into DNA with the normal gene through the process of homologous recombination. The iPS cells then differentiated into blood stem cells, or hematopoietic stem cells. The hematopoietic cells were injected back into the infected mice, where they proliferate and differentiate into normal blood cells, curing the mice of the disease.[3][4][verification needed]
To determine whether the mice were cured from the disease, the scientists checked for the usual symptoms of sickle cell disease. They examined the blood for mean corpuscular volume (MCV) and red cell distribution width (RDW) and urine concentration defects. They also checked for sickled red blood cells. They examined the DNA through gel electrophoresis, checking for bands that display an allele that causes sickling. Compared to the untreated mice with the disease, which they used as a control, "the treated animals had marked increases in RBC counts, healthy hemoglobin, and packed cell volume levels".[5]
Researchers examined "the urine concentration defect, which results from RBC sickling in renal tubules and consequent reduction in renal medullary blood flow, and the general deteriorated systemic condition reflected by lower body weight and increased breathing."[5] They were able to see that these parts of the body of the mice had healed or improved. This indicated that "all hematological and systemic parameters of sickle cell anemia improved substantially and were comparable to those in control mice."[5] They cannot say if this will work in humans because a safe way to inject the genes for the induced pluripotent cells is still needed.[citation needed]
The reprogramming of the induced pluripotent stem cells in mice was successfully duplicated in humans within a year of the successful experiment on the mice. This reprogramming was done in several labs and it was shown that the iPS cells in humans were almost identical to original embryonic stem cells (ES cells) that are responsible for the creation of all structures in a fetus.[1] An important feature of iPS cells is that they can be generated with cells taken from an adult, which would circumvent many of the ethical problems associated with working with ES cells. These iPS cells also have potential in creating and examining new disease models and developing more efficient drug treatments.[6] Another feature of these cells is that they provide researchers with a human cell sample, as opposed to simply using an animal with similar DNA, for drug testing.
One major problem with iPS cells is the way in which the cells are reprogrammed. Using gene-carrying viruses has the potential to cause iPS cells to develop into cancerous cells.[1] Also, an implant made using undifferentiated iPS cells, could cause a teratoma to form. Any implant that is generated from using these iPS cells would only be viable for transplant into the original subject that the cells were taken from. In order for these iPS cells to become viable in therapeutic use, there are still many steps that must be taken.[5][7]
In the future, researchers hope that induced pluripotent cells may be used to treat other diseases. Pluripotency is a crucial part of disease treatment because iPS cells are capable of differentiation in a way that is very similar to embryonic stem cells which can grow into fully differentiated tissues. iPS cells also demonstrate high telomerase activity and express human telomerase reverse transcriptase, a necessary component in the telomerase protein complex. Also, iPS cells expressed cell surface antigenic markers expressed on ES cells. Also, doubling time and mitotic activity are cornerstones of ES cells, as stem cells must self-renew as part of their definition. As said, iPS cells are morphologically similar to embryonic stem cells. Each cell has a round shape, a large nucleolus and a small amount of cytoplasm. One day, the process may be used in practical settings to provide a fundamental way of regeneration.
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Induced pluripotent stem-cell therapy - Wikipedia
Supercourse: Epidemiology, the Internet, and Global Health
By LizaAVILA
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Supercourse: Epidemiology, the Internet, and Global Health
spinal cord injury, embryonic stem cells, paralysis, pain …
By LizaAVILA
SAN FRANCISCO Researchers have successfully transplanted healthy human cells into mice with spinal cord injuries, bringing the world one step closer to easing the chronic pain and incontinence suffered by people with paralysis.
The research team did not focus on restoring the rodents ability to walk; rather, it helped remedy these two other debilitating side effects of spinal cord injury.
If successful in humans, thefindingscould someday ease the lives of those with these distressing conditions, said Dr. Arnold Kriegstein, co-senior author of the study and director of the Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research at UC San Francisco. The research was published in Thursdays issue of the journal Cell Stem Cell.
This is a very important step, Kriegstein said. The treated animals improved in pain relief and bladder function.The research offers the promising potential of using a new therapeutic approach cell therapy to repair damaged neural tissue, showing that new cells can be integrated into an injured spinal cord.
A similar approach also has helped mice with epilepsy and Parkinsons disease.
More than aquarter of a million Americans live with spinal cord injuries, and 17,000 new cases occur each year, according to the National Spinal Cord Injury Statistical Center. More than half of those people go on to develop chronic pain in their limbs, called neuropathy. And nearly all develop bladder problems, which can result in kidney damage.
The spinal cord is the major highway for nerve cells to relay information between the brain and the rest of the body. When the spinal cord is injured, tears and inflammation harm surrounding cells.
The field has been very focused on restoring patients ability to walk, perhaps because thats often their most visible impairment, study co-authorLinda Noble-Haeusslein, a professor of physical therapy and rehabilitation at UCSF, said in a statement.
But a recent study showing that patients complained of pain and loss of bladder control more than paralysis suggested that we had really missed the boat as a field, she said. It caused us to dramatically shift what we do in the lab.
The cells used in the study, called neurons, were grown from human embryonic stem cells the bodys building blocks, capable of generating more than1,000 different types of adult cells.
They arent just any garden-variety neuron. These cells have the ability to inhibit, rather than excite, the neural network of the spine. Thats important because the pain and loss of bladder control are believed to be caused by overactivated neural circuits.
The healthy body keeps this excitable circuitry under control.But inflammation caused by a spinal cord injury causes a loss of this control.
The UCSF team grew the replacement cells in a South San Francisco biotech lab ofNeurona Therapeutics, founded by study co-authorCory Nicholasand Kriegstein, UCSFprofessor of developmental and stem cell biology. The company hopes to mass-produce these cells for use in future clinical trials.
They injected the young human cells into the spines of mice about two weeks afterinjury. They targeted the thoracic region about halfway up the spinal cord because thats a common site of injury for humans.But they were careful not to inject the young cells directly into the injured areas because that is a toxic place full of inflammation.
Remarkably, over the next six months the human cells matured, migrated toward the site of the injury and made connections with the spinal cords of the mice.
Compared to untreated mice, the treated rodents showed significantly less hypersensitivity to touch and painful stimuli and reduced abnormal scratching. Treated mice also had improved bladder function and produced more normal, voluntary patterns of urination in their cages.
A different research team is focusing on a fix for paralysis. This necessitatesa different strategy, requiring treatment with stem cell-derived neurons whose job it is to conduct electrical impulses down the spine. And these cells may face a more daunting environment if injected directly into injured areas.
The first trial by Geron Corp. stalled in late 2011, mostly because of financial concerns. But a Fremont-based biotech company calledAsterias Biotherapeutics, a subsidiary of BioTime, bought Gerons intellectual property and is continuing the research. It recently received approval fromthe U.S. Food and Drug Administration for a safety and early trial of the cells for treating spinal cord injury.
Meanwhile, the UCSF team is working to replicate their findings of improved bladder control and chronic pain. And they seek to learn the best time to inject the cells. Funders for the research included the National Institutes of Health and the California Institute of Regenerative Medicine.
The team is hoping to scale up their production of their specialized cells with the goal of entering human trials, after proving to the FDA that their effort is safe.
We are eager to move in that direction as quickly as we can, Kriegstein said.
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spinal cord injury, embryonic stem cells, paralysis, pain ...
How Does A Heart Defect Start? Stanford Scientists Use …
By LizaAVILA
For years, pediatric cardiologists have been trying to understand the origin of a puzzling structural defect of the heart muscle wall, a congenital problem called left ventricular non-compaction(LVNC). In people with this defect, the muscle of the hearts biggest pumping chamber looks spongy rather than smooth and solid.
For such congenital cardiomyopathies, currently there is no effective therapy, and the only cure is heart transplantation, said StanfordsJoseph Wu, MD, PhD, a cardiologist who led a new study of the condition that published online this week inNature Cell Biology.
His team was looking for a new way to address a very old research problem: They didnt know how much they could trust studies done on animal models of the disease. Mouse and rat models of LVNC also have spongy heart muscle, but its not clear if their defect starts the same way as in humans, nor whether findings from rodent studies could help treat humans.
So Wus team used innovative stem cell techniques instead. They took skin and blood cells donated by four members of a family affected by LVNC and converted them into induced pluripotent stem cells, which are stem cells made in a lab from adult cells. Using these stem cells, the researchers then made human heart muscle cells that they could study in a dish. That gave them a way to study what was happening in patients hearts without taking heart muscle biopsies.
Before starting their work, the researchers already knew that LVNC begins long before birth, when the heart muscle fails to make an important developmental shift. In the earliest stages of cardiac development, its normal for the muscle to be spongy. At about 8 weeks of gestation, the human heart muscle is supposed to compress into a thick, compact mass, but that shift doesnt happen correctly in LVNC patients. Earlier studies gave conflicting information about why: maybe the heart muscle cells were proliferating too little, or maybe too much.
Another mystery about the disease is its range of severity, which varies from no symptoms at all to complete heart failure. As the new paper describes, the family who agreed to have their cells studied is a good example. Of three siblings who donated cells for research, one had already had a heart transplant, while the other two had hearts that pumped normally in spite of deeper trabeculations (the scientific word for the spongy formations). Meanwhile, their father had an enlarged heart, but no sponginess in his heart muscle and no other symptoms.
Using the heart muscle cells derived from all four people, the researchers identified the gene defect that causes LVNC in this family; it codes for a cardiac transcription factor or a protein that controls the expression of other genes called TBX20. The scientists conducted several experiments to figure out how the TBX20 abnormality changes heart muscle cell proliferation with the abnormality, the cells dont proliferate enough, it turns out. They also explored the exact signaling pathways that cause the problem, showing that the magnitude of signaling abnormalities could explain differences in symptom severity between family members. They created a mouse model with the familys gene defect for further characterization, and also showed that blocking the faulty signal from the altered TBX20 could restore the mutated cells ability to proliferate. Its possible that some day, they might be able to turn these findings into a drug that could correct heart muscle formation in affected fetuses before birth.
The new findings still leave unanswered questions about the origins of LVNC. Cardiologists suspect the problem can arise in several ways, and theyll need to study many more families to find out if TBX20 mutations are a common or rare cause. But the paper does demonstrate how induced pluripotent stem cells can overcome a research hurdle, and suggests that the same methods could help scientists tackling other hard-to-study conditions.
This study shows the feasibility of modeling such developmental defects using human tissue-specific cells, rather than relying on animal cells or animal models, Wu said. It opens up an exciting new avenue for research into congenital heart disease that could help literally the youngest in utero patients.
Previously: One of the most promising minds of his generation: Joseph Wu takes stem cells to heart, Stem cells create faithful replicas of native tissue, according to Stanford study and A cheaper, faster way to find genetic defects in heart patients Photo by amanda tipton
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How Does A Heart Defect Start? Stanford Scientists Use ...
Cell Therapy Ltd
By LizaAVILA
Founded in 2009 by Nobel prize winner Professor Sir Martin Evans and Ajan Reginald, former Global Head of Emerging Technologies at Roche, CTL develops life-saving and life altering regenerative medicines. CTLs team of scientists, physicians, and experienced management have discovered and developed a pipeline of world-class regenerative medicines.
Sir Martin Evans' unique expertise in discovering rare stem cells led to CTLs innovative drug discovery engine that can uniquely isolate very rare and potent tissue specific stem cells. This exceptional class of cells is then engineered into unique disease-specific cellular regenerative medicines. Each medicine is disease specific and forms part of CTLs world-class portfolio of four off the shelf blockbuster medicines all scheduled for launch before 2020.
The products in late stage clinical trials include Heartcel which regenerates the damaged heart of adults with coronary artery malformations and children with Kawasaki Disease and Bland White Garland Syndrome. In 2014, Heartcel reported unprecedented heart regeneration clinical trial results and is scheduled to launch in 2018 to treat ~400,000 patients worldwide. Myocardion is in Phase II/III trials and treats mild-moderate heart failure affecting 10 million patients worldwide. Tendoncel is the worlds first topical regenerative medicine, for early intervention of severe tendon injuries, and has completed Phase II trials. It is designed to treat the >1 million severe tendon injuries each year in the US and Europe. Skincel is for skin regeneration, and is due to complete Phase II trials in 2015. It is designed to address ulceration and wrinkles.
CTL combines world-class science and management expertise to bring life-saving regenerative medicines to market.
European Society of Gene and Cell Therapy Congress, 17-20 September 2015, Helsinki,Finland (ESGCT 2015)
4th International Conference and Exhibition on Cell & Gene Therapy, August 10-12, 2015, London (CGT 2015)
The International Society for Stem Cell Research Annual Meeting, 24th-27th June 2015, Stockholm, Sweden (ISSCR 2015)
British Society for Gene and Cell Therapy Annual Conference, 9th-11th June 2015, Strathclyde, Glasgow (BSGCT 2015)
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Cell Therapy Ltd
Hematopoietic stem cell transplantation – Wikipedia, the …
By LizaAVILA
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 may be autologous (the patient's own stem cells are used) or allogeneic (the stem cells come from a donor). It is a medical procedure in the field of hematology, 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 are major complications of allogeneic HSCT.
Hematopoietic stem cell transplantation remains a dangerous procedure with many possible complications; it is reserved for patients with life-threatening diseases. As survival following the procedure has increased, its use has expanded beyond cancer, such as autoimmune diseases.[1][2]
Indications for stem cell transplantation are as follows:
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, "mini transplant(microtransplantation)," 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 percent) were autologous and 21,516 (43 percent) were allogeneic (11,928 from family donors and 9,588 from unrelated donors). The main indications for transplant were lymphoproliferative disorders (54.5 percent) and leukemias (33.8 percent), and the majority took place in either Europe (48 percent) or the Americas (36 percent).[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 cancers 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]
Allogeneics 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.[16]
As of 2013[update], there were at least two commercialized allogeneic cell therapies, Prochymal and Cartistem.[17]
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.
Peripheral blood stem cells[18] are now the most common source of stem cells for allogeneic HSCT. They are collected from the blood through a process known as apheresis. The donor's blood is withdrawn through a sterile needle in one arm and passed through a machine that removes white blood cells. The red blood cells are returned to the donor. The peripheral stem cell yield is boosted with daily subcutaneous injections of Granulocyte-colony stimulating factor, serving to mobilize stem cells from the donor's bone marrow into the peripheral circulation.
It is also possible to extract stem cells from amniotic fluid for both autologous or heterologous use at the time of childbirth.
Umbilical cord blood is obtained when a mother donates her infant's umbilical cord and placenta after birth. Cord blood has a higher concentration of HSC than is normally found in adult blood. However, the small quantity of blood obtained from an Umbilical Cord (typically about 50 mL) makes it more suitable for transplantation into small children than into adults. Newer techniques using ex-vivo expansion of cord blood units or the use of two cord blood units from different donors allow cord blood transplants to be used in adults.
Cord blood can be harvested from the Umbilical Cord of a child being born after preimplantation genetic diagnosis (PGD) for human leucocyte antigen (HLA) matching (see PGD for HLA matching) in order to donate to an ill sibling requiring HSCT.
Unlike other organs, bone marrow cells can be frozen (cryopreserved) for prolonged periods without damaging too many cells. This is a necessity with autologous HSC because the cells must be harvested from the recipient months in advance of the transplant treatment. In the case of allogeneic transplants, fresh HSC are preferred in order to avoid cell loss that might occur during the freezing and thawing process. Allogeneic cord blood is stored frozen at a cord blood bank because it is only obtainable at the time of childbirth. To cryopreserve HSC, a preservative, DMSO, must be added, and the cells must be cooled very slowly in a controlled-rate freezer to prevent osmotic cellular injury during ice crystal formation. HSC may be stored for years in a cryofreezer, which typically uses liquid nitrogen.
The chemotherapy or irradiation given immediately prior to a transplant is called the conditioning regimen, the purpose of which is to help eradicate the patient's disease prior to the infusion of HSC and to suppress immune reactions. The bone marrow can be ablated (destroyed) with dose-levels that cause minimal injury to other tissues. In allogeneic transplants a combination of cyclophosphamide with total body irradiation is conventionally employed. This treatment also has an immunosuppressive effect that prevents rejection of the HSC by the recipient's immune system. The post-transplant prognosis often includes acute and chronic graft-versus-host disease that may be life-threatening. However, in certain leukemias this can coincide with protection against cancer relapse owing to the graft versus tumor effect.[19]Autologous transplants may also use similar conditioning regimens, but many other chemotherapy combinations can be used depending on the type of disease.
A newer treatment approach, non-myeloablative allogeneic transplantation, also termed reduced-intensity conditioning (RIC), uses doses of chemotherapy and radiation too low to eradicate all the bone marrow cells of the recipient.[20]:320321 Instead, non-myeloablative transplants run lower risks of serious infections and transplant-related mortality while relying upon the graft versus tumor effect to resist the inherent increased risk of cancer relapse.[21][22] Also significantly, while requiring high doses of immunosuppressive agents in the early stages of treatment, these doses are less than for conventional transplants.[23] This leads to a state of mixed chimerism early after transplant where both recipient and donor HSC coexist in the bone marrow space.
Decreasing doses of immunosuppressive therapy then allows donor T-cells to eradicate the remaining recipient HSC and to induce the graft versus tumor effect. This effect is often accompanied by mild graft-versus-host disease, the appearance of which is often a surrogate marker for the emergence of the desirable graft versus tumor effect, and also serves as a signal to establish an appropriate dosage level for sustained treatment with low levels of immunosuppressive agents.
Because of their gentler conditioning regimens, these transplants are associated with a lower risk of transplant-related mortality and therefore allow patients who are considered too high-risk for conventional allogeneic HSCT to undergo potentially curative therapy for their disease. The optimal conditioning strategy for each disease and recipient has not been fully established, but RIC can be used in elderly patients unfit for myeloablative regimens, for whom a higher risk of cancer relapse may be acceptable.[20][22]
After several weeks of growth in the bone marrow, expansion of HSC and their progeny is sufficient to normalize the blood cell counts and re-initiate the immune system. The offspring of donor-derived hematopoietic stem cells have been documented to populate many different organs of the recipient, including the heart, liver, and muscle, and these cells had been suggested to have the abilities of regenerating injured tissue in these organs. However, recent research has shown that such lineage infidelity does not occur as a normal phenomenon[citation needed].
HSCT is associated with a high treatment-related mortality in the recipient (1 percent or higher)[citation needed], which limits its use to conditions that are themselves life-threatening. Major complications are veno-occlusive disease, mucositis, infections (sepsis), graft-versus-host disease and the development of new malignancies.
Bone marrow transplantation usually requires that the recipient's own bone marrow be destroyed ("myeloablation"). Prior to "engraftment" patients may go for several weeks without appreciable numbers of white blood cells to help fight infection. This puts a patient at high risk of infections, sepsis and septic shock, despite prophylactic antibiotics. However, antiviral medications, such as acyclovir and valacyclovir, are quite effective in prevention of HSCT-related outbreak of herpetic infection in seropositive patients.[24] The immunosuppressive agents employed in allogeneic transplants for the prevention or treatment of graft-versus-host disease further increase the risk of opportunistic infection. Immunosuppressive drugs are given for a minimum of 6-months after a transplantation, or much longer if required for the treatment of graft-versus-host disease. Transplant patients lose their acquired immunity, for example immunity to childhood diseases such as measles or polio. For this reason transplant patients must be re-vaccinated with childhood vaccines once they are off immunosuppressive medications.
Severe liver injury can result from hepatic veno-occlusive disease (VOD). Elevated levels of bilirubin, hepatomegaly and fluid retention are clinical hallmarks of this condition. There is now a greater appreciation of the generalized cellular injury and obstruction in hepatic vein sinuses, and hepatic VOD has lately been referred to as sinusoidal obstruction syndrome (SOS). Severe cases of SOS are associated with a high mortality rate. Anticoagulants or defibrotide may be effective in reducing the severity of VOD but may also increase bleeding complications. Ursodiol has been shown to help prevent VOD, presumably by facilitating the flow of bile.
The injury of the mucosal lining of the mouth and throat is a common regimen-related toxicity following ablative HSCT regimens. It is usually not life-threatening but is very painful, and prevents eating and drinking. Mucositis is treated with pain medications plus intravenous infusions to prevent dehydration and malnutrition.
Graft-versus-host disease (GVHD) is an inflammatory disease that is unique to allogeneic transplantation. It is an attack of the "new" bone marrow's immune cells against the recipient's tissues. This can occur even if the donor and recipient are HLA-identical because the immune system can still recognize other differences between their tissues. It is aptly named graft-versus-host disease because bone marrow transplantation is the only transplant procedure in which the transplanted cells must accept the body rather than the body accepting the new cells. Acute graft-versus-host disease typically occurs in the first 3 months after transplantation and may involve the skin, intestine, or the liver. High-dose corticosteroids such as prednisone are a standard treatment; however this immuno-suppressive treatment often leads to deadly infections. Chronic graft-versus-host disease may also develop after allogeneic transplant. It is the major source of late treatment-related complications, although it less often results in death. In addition to inflammation, chronic graft-versus-host disease may lead to the development of fibrosis, or scar tissue, similar to scleroderma; it may cause functional disability and require prolonged immunosuppressive therapy. Graft-versus-host disease is usually mediated by T cells, which react to foreign peptides presented on the MHC of the host[citation needed].
Graft versus tumor effect (GVT) or "graft versus leukemia" effect is the beneficial aspect of the Graft-versus-Host phenomenon. For example, HSCT patients with either acute, or in particular chronic, graft-versus-host disease after an allogeneic transplant tend to have a lower risk of cancer relapse.[25][26] This is due to a therapeutic immune reaction of the grafted donor T lymphocytes against the diseased bone marrow of the recipient. This lower rate of relapse accounts for the increased success rate of allogeneic transplants, compared to transplants from identical twins, and indicates that allogeneic HSCT is a form of immunotherapy. GVT is the major benefit of transplants that do not employ the highest immuno-suppressive regimens.
Graft versus tumor is mainly beneficial in diseases with slow progress, e.g. chronic leukemia, low-grade lymphoma, and some cases multiple myeloma. However, it is less effective in rapidly growing acute leukemias.[27]
If cancer relapses after HSCT, another transplant can be performed, infusing the patient with a greater quantity of donor white blood cells (Donor lymphocyte infusion).[27]
Patients after HSCT are at a higher risk for oral carcinoma. Post-HSCT oral cancer may have more aggressive behavior with poorer prognosis, when compared to oral cancer in non-HSCT patients.[28]
Prognosis in HSCT varies widely dependent upon disease type, stage, stem cell source, HLA-matched status (for allogeneic HCST) and conditioning regimen. A transplant offers a chance for cure or long-term remission if the inherent complications of graft versus host disease, immuno-suppressive treatments and the spectrum of opportunistic infections can be survived.[13][14] In recent years, survival rates have been gradually improving across almost all populations and sub-populations receiving transplants.[29]
Mortality for allogeneic stem cell transplantation can be estimated using the prediction model created by Sorror et al.,[30] using the Hematopoietic Cell Transplantation-Specific Comorbidity Index (HCT-CI). The HCT-CI was derived and validated by investigators at the Fred Hutchinson Cancer Research Center (Seattle, WA). The HCT-CI modifies and adds to a well-validated comorbidity index, the Charlson Comorbidity Index (CCI) (Charlson et al.[31]) The CCI was previously applied to patients undergoing allogeneic HCT but appears to provide less survival prediction and discrimination than the HCT-CI scoring system.
The risks of a complication depend on patient characteristics, health care providers and the apheresis procedure, and the colony-stimulating factor used (G-CSF). G-CSF drugs include filgrastim (Neupogen, Neulasta), and lenograstim (Graslopin).
Filgrastim is typically dosed in the 10 microgram/kg level for 45 days during the harvesting of stem cells. The documented adverse effects of filgrastim include splenic rupture (indicated by left upper abdominal or shoulder pain, risk 1 in 40000), Adult respiratory distress syndrome (ARDS), alveolar hemorrage, and allergic reactions (usually expressed in first 30 minutes, risk 1 in 300).[32][33][34] In addition, platelet and hemoglobin levels dip post-procedure, not returning to normal until one month.[34]
The question of whether geriatrics (patients over 65) react the same as patients under 65 has not been sufficiently examined. Coagulation issues and inflammation of atherosclerotic plaques are known to occur as a result of G-CSF injection.[33] G-CSF has also been described to induce genetic changes in mononuclear cells of normal donors.[33] There is evidence that myelodysplasia (MDS) or acute myeloid leukaemia (AML) can be induced by GCSF in susceptible individuals.[35]
Blood was drawn peripherally in a majority of patients, but a central line to jugular/subclavian/femoral veins may be used in 16 percent of women and 4 percent of men. Adverse reactions during apheresis were experienced in 20 percent of women and 8 percent of men, these adverse events primarily consisted of numbness/tingling, multiple line attempts, and nausea.[34]
A study involving 2408 donors (1860 years) indicated that bone pain (primarily back and hips) as a result of filgrastim treatment is observed in 80 percent of donors by day 4 post-injection.[34] This pain responded to acetaminophen or ibuprofen in 65 percent of donors and was characterized as mild to moderate in 80 percent of donors and severe in 10 percent.[34] Bone pain receded post-donation to 26 percent of patients 2 days post-donation, 6 percent of patients one week post-donation, and <2 percent 1 year post-donation. Donation is not recommended for those with a history of back pain.[34] Other symptoms observed in more than 40 percent of donors include myalgia, headache, fatigue, and insomnia.[34] These symptoms all returned to baseline 1 month post-donation, except for some cases of persistent fatigue in 3 percent of donors.[34]
In one metastudy that incorporated data from 377 donors, 44 percent of patients reported having adverse side effects after peripheral blood HSCT.[35] Side effects included pain prior to the collection procedure as a result of GCSF injections, post-procedural generalized skeletal pain, fatigue and reduced energy.[35]
A study that surveyed 2408 donors found that serious adverse events (requiring prolonged hospitalization) occurred in 15 donors (at a rate of 0.6 percent), although none of these events were fatal.[34] Donors were not observed to have higher than normal rates of cancer with up to 48 years of follow up.[34] One study based on a survey of medical teams covered approximately 24,000 peripheral blood HSCT cases between 1993 and 2005, and found a serious cardiovascular adverse reaction rate of about 1 in 1500.[33] This study reported a cardiovascular-related fatality risk within the first 30 days HSCT of about 2 in 10000. For this same group, severe cardiovascular events were observed with a rate of about 1 in 1500. The most common severe adverse reactions were pulmonary edema/deep vein thrombosis, splenic rupture, and myocardial infarction. Haematological malignancy induction was comparable to that observed in the general population, with only 15 reported cases within 4 years.[33]
Georges Math, a French oncologist, performed the first European bone marrow transplant in November 1958 on five Yugoslavian nuclear workers whose own marrow had been damaged by irradiation caused by a criticality accident at the Vina Nuclear Institute, but all of these transplants were rejected.[36][37][38][39][40] Math later pioneered the use of bone marrow transplants in the treatment of leukemia.[40]
Stem cell transplantation was pioneered using bone-marrow-derived stem cells by a team at the Fred Hutchinson Cancer Research Center from the 1950s through the 1970s led by E. Donnall Thomas, whose work was later recognized with a Nobel Prize in Physiology or Medicine. Thomas' work showed that bone marrow cells infused intravenously could repopulate the bone marrow and produce new blood cells. His work also reduced the likelihood of developing a life-threatening complication called graft-versus-host disease.[41]
The first physician to perform a successful human bone marrow transplant on a disease other than cancer was Robert A. Good at the University of Minnesota in 1968.[42] In 1975, John Kersey, M.D., also of the University of Minnesota, performed the first successful bone marrow transplant to cure lymphoma. His patient, a 16-year-old-boy, is today the longest-living lymphoma transplant survivor.[43]
At the end of 2012, 20.2 million people had registered their willingness to be a bone marrow donor with one of the 67 registries from 49 countries participating in Bone Marrow Donors Worldwide. 17.9 million of these registered donors had been ABDR typed, allowing easy matching. A further 561,000 cord blood units had been received by one of 46 cord blood banks from 30 countries participating. The highest total number of bone marrow donors registered were those from the USA (8.0 million), and the highest number per capita were those from Cyprus (15.4 percent of the population).[44]
Within the United States, racial minority groups are the least likely to be registered and therefore the least likely to find a potentially life-saving match. In 1990, only six African-Americans were able to find a bone marrow match, and all six had common European genetic signatures.[45]
Africans are more genetically diverse than people of European descent, which means that more registrations are needed to find a match. Bone marrow and cord blood banks exist in South Africa, and a new program is beginning in Nigeria.[45] Many people belonging to different races are requested to donate as there is a shortage of donors in African, Mixed race, Latino, Aboriginal, and many other communities.
In 2007, a team of doctors in Berlin, Germany, including Gero Htter, performed a stem cell transplant for leukemia patient Timothy Ray Brown, who was also HIV-positive.[46] From 60 matching donors, they selected a [CCR5]-32 homozygous individual with two genetic copies of a rare variant of a cell surface receptor. This genetic trait confers resistance to HIV infection by blocking attachment of HIV to the cell. Roughly one in 1000 people of European ancestry have this inherited mutation, but it is rarer in other populations.[47][48] The transplant was repeated a year later after a leukemia relapse. Over three years after the initial transplant, and despite discontinuing antiretroviral therapy, researchers cannot detect HIV in the transplant recipient's blood or in various biopsies of his tissues.[49] Levels of HIV-specific antibodies have also declined, leading to speculation that the patient may have been functionally cured of HIV. However, scientists emphasise that this is an unusual case.[50] Potentially fatal transplant complications (the "Berlin patient" suffered from graft-versus-host disease and leukoencephalopathy) mean that the procedure could not be performed in others with HIV, even if sufficient numbers of suitable donors were found.[51][52]
In 2012, Daniel Kuritzkes reported results of two stem cell transplants in patients with HIV. They did not, however, use donors with the 32 deletion. After their transplant procedures, both were put on antiretroviral therapies, during which neither showed traces of HIV in their blood plasma and purified CD4 T cells using a sensitive culture method (less than 3 copies/mL). However, the virus was once again detected in both patients some time after the discontinuation of therapy.[53]
Since McAllister's 1997 report on a patient with multiple sclerosis (MS) who received a bone marrow transplant for CML,[54] there have been over 600 reports of HSCTs performed primarily for MS.[55] These have been shown to "reduce or eliminate ongoing clinical relapses, halt further progression, and reduce the burden of disability in some patients" that have aggressive highly active MS, "in the absence of chronic treatment with disease-modifying agents".[55]
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Hematopoietic stem cell transplantation - Wikipedia, the ...
Cell Therapy & Regenerative Medicine – University of Utah …
By LizaAVILA
About Us
Learn more about Cell Therapy & Regenerative Medicine.
What is a Neurosphere?
CTRM provides services to develop and manufacture novel cellular therapy.
The Cell Therapy and Regenerative Medicine Program (CTRM) at the University of Utah provides the safest, highest quality products for therapeutic use and research. Our goals are to facilitate the availability of cellular and tissue based therapies to patients by bridging efforts in basic research, bioengineering and the medical sciences. As well as assemble the expertise and infrastructure to address the complex regulatory, financial and manufacturing challenges associated with delivering cell and tissue based products to patients.
To support hematopoietic stem cell transplants and to deliver innovative cellular and tissue engineered products to patients by providing comprehensive bench to bedside services that coordinate the efforts of clinicians, researchers, and bioengineers.
Product quality, safety and efficacy; Optimization of resource utilization; Promotion of productive collaborations; Support of innovative products; and Adherence to scientific and ethical excellence.
The Center of Excellence for the state of Utah that translates cutting-edge cell therapy and engineered tissue based research into clinical products that extend and improve the quality of life of individuals suffering from debilitating diseases and injuries.
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Cell Therapy & Regenerative Medicine - University of Utah ...
Going viral: chimeric antigen receptor T-cell therapy for …
By LizaAVILA
On July 1, 2014, the United States Food and Drug Administration granted 'breakthrough therapy' designation to CTL019, the anti-CD19 chimeric antigen receptor T-cell therapy developed at the University of Pennsylvania. This is the first personalized cellular therapy for cancer to be so designated and occurred 25 years after the first publication describing genetic redirection of T cells to a surface antigen of choice. The peer-reviewed literature currently contains the outcomes of more than 100 patients treated on clinical trials of anti-CD19 redirected T cells, and preliminary results on many more patients have been presented. At last count almost 30 clinical trials targeting CD19 were actively recruiting patients in North America, Europe, and Asia. Patients with high-risk B-cell malignancies therefore represent the first beneficiaries of an exciting and potent new treatment modality that harnesses the power of the immune system as never before. A handful of trials are targeting non-CD19 hematological and solid malignancies and represent the vanguard of enormous preclinical efforts to develop CAR T-cell therapy beyond B-cell malignancies. In this review, we explain the concept of chimeric antigen receptor gene-modified T cells, describe the extant results in hematologic malignancies, and share our outlook on where this modality is likely to head in the near future.
2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
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Going viral: chimeric antigen receptor T-cell therapy for ...
Regenerative Medicine and Stem cell based Cell therapies …
By LizaAVILA
Information contained on this page is provided by an independent third-party content provider. WorldNow and this Station make no warranties or representations in connection therewith. If you have any questions or comments about this page please contact pressreleases@worldnow.com.
SOURCE Reportlinker
NEW YORK, Oct. 1, 2015 /PRNewswire/ -- Innovative Therapies for treating diseases are being sought after with fresh vigor as new targets, approaches and biology is discovered. Improved health care, nutrition and preventive medicine in the last few decades have all helped in increasing the life expectancy WW. However, this has not translated into any reduction in the incidence or prevalence of chronic or critical illnesses! On the contrary the incidence of chronic diseases like diabetes, obesity, arthritis etc. as well as cancer and the maladies associated with aging (dementia, Alzheimer's etc.) are on the rise!. Consequently the pharma industry continues to grow and is projected to
achieve sales in excess of trillion dollar mark by 2020 By the next decade, one field which is poised to bring a paradigm change in the way diseases are treated is the Stem cell therapy/Regenerative Medicine space. The number of companies and products in the clinic have reached a critical mass warranting a close watch for those interested in keeping pace with the development of new medicines.
Regenerative Medicine and Stem cell based Cell therapies-Drugs of the Future Offering Hope for Cure
EXECUTIVE SUMMARY
- INTRODUCTION
- Tough Choice- "Autologous vs. Allogenic " Therapies
- REGULATORY GUIDELINES
- Marketed Cell based/Stem Cell Products
- Progress and Challenges
- Progress in Specific Therapy Areas
- SELECT UPCOMING MILESTONES IN REGENERATIVE MEDICINE/STEM
CELL FOCUSED COMPANIES (2015-16)
- Appendix
Read the full report: http://www.reportlinker.com/p02629094-summary/view-report.html
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To view the original version on PR Newswire, visit:http://www.prnewswire.com/news-releases/regenerative-medicine-and-stem-cell-based-cell-therapies-drugs-of-the-future-offering-hope-for-cure-300153074.html
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How are stem cells used in medicine today? – HowStuffWorks
By LizaAVILA
From the United States Senate to houses of worship, and even to the satirical television show "South Park," stem cells have been in the spotlight -- though not always in the kindest light. Since early research has focused on the use of embryonic stem cells (cells less than a week old), the very act of extracting these cells has raised a raft of ethical questions for researchers and the medical community at large, with federal funding often hanging in the balance.
However, the advances in stem cell research and the subsequent applications to modern medicine can't be ignored. According to the National Institutes of Health (NIH), stem cells are being considered for a wide variety of medical procedures, ranging from cancer treatment to heart disease and cell-based therapies for tissue replacement.
Why? To answer that question, you have to understand what stem cells are. Called "master" cells or "a sort of internal repair system," these remarkable-yet-unspecialized cells are able to divide, seemingly without limits, to help mend or replenish other living cells [sources: Mayo Clinic; NIH]. In short, these cells are the cellular foundation of the entire human body, or literally the body's building blocks.
By studying these cells and how they develop, researchers are closing in on a better understanding of how our bodies grow and mature, and how diseases and other abnormalities take root. The research work that began with mouse embryos in the early 1980s eventually helped scientists devise a way to isolate stem cells from human embryos by the late 1990s.
Embryonic, or pluripotent, stem cells are taken from human embryos that are less than a week old. These cells are wildly versatile, capable of dividing into more stem cells or becoming any type of cell in the human body (roughly 220 types, including muscle, nerve, blood, bone and skin). Researchers have also recently found stem cells in amniotic fluid taken from pregnant women during amniocentesis, a fairly routine procedure used to determine potential complications, such as Down syndrome.
However, recent research has indicated that adult stem cells, once thought to be more limited in their capabilities, are actually much more versatile than originally believed. Though not as "pure" as embryonic stem cells, due to environmental conditions that exist in the real world -- ranging from air pollution to food impurities -- adult stem cells are nonetheless garnering attention, if only because they don't incite the same ethical debate as embryonic stem cells.
So, what are the cutting-edge uses for stem cells?
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How are stem cells used in medicine today? - HowStuffWorks
Apple Stem Cells – Sonya Dakar Skin Clinic
By LizaAVILA
WHAT ARE STEM CELLS?
Stem cells are super unique in that they have the ability to go through numerous cycles and cell divisions while maintaining the undifferentiated state. Primarily, stem cells are capable of self-renewal and can transform themselves into other cell types of the same tissue. Their crucial role is to replenish dying cells and regenerate damaged tissue. Stem cells have a limited life expectation due to environmental and intrinsic stress factors. Because their life is endangered by internal and external stresses, stem cells have to be protected and supported to delay preliminary aging. In aged bodies, the number and activity of stem cells in reduced.
Until several years ago, the tart, unappealing breed of the Swiss-grown Uttwiler Sptlauber apples, did not seem to offer anything of value. That was until Swiss scientists discovered the unusual longevity of the stem cells that kept these apples alive months after other apples shriveled and fell off their trees. In the rural region of Switzerland, home of these magical apples, it was discovered that when the unpicked apples or tree bark was punctured, Swiss Apple trees have the ability to heal themselves and last longer than other varieties. What was the secret to these apples prolonged lives?
These scientists got to work to find out. What they revealed was that apple stem cells work just like human stem cells, they work to maintain and repair skin tissue. The main difference is that unlike apple stem cells, skin stem cells do not have a long lifespan, and once they begin depleting, the signs of aging start kicking in (in the forms of loose skin, wrinkles, the works). Time to harness these apple stem cells into anti aging skin care! Not so fast. As mentioned, Uttwiler Sptlauber apples are now very rare to the point that the extract can no longer be made in a traditional fashion. The great news is that scientists developed a plant cell culture technology, which involves breeding the apple stem cells in the laboratory.
Human stem cells on the skins epidermis are crucial to replenish the skin cells that are lost due to continual shedding. When epidermal stem cells are depleted, the number of lost or dying skin cells outpaces the production of new cells, threatening the skins health and appearance.
Like humans, plants also have stem cells. Enter the stem cells of the Uttwiler Sptlauber apple tree, whose fruit demonstrates an exceptionally long shelf-life. How can these promising stem cells help our skin?
Studies show that apple stem cells boosts production of human stem cells, protect the cell from stress, and decreases wrinkles. How does it work? The internal fluid of these plant cells contains components that help to protect and maintain human stem cells. Apple stem cells contain metabolites to ensure longevity as the tree is known for the fact that its fruit keep well over long periods of time.
When tested in vitro, the apple stem cell extract was applied to human stem cells from umbilical cords and was found to increase the number of the stem cells in culture. Furthermore, the addition of the ingredient to umbilical cord stem cells appeared to protect the cells from environmental stress such as UV light.
Apple stem cells do not have to be fed through the umbilical cord to benefit our skin! The extract derived from the plant cell culture technology is being harnessed as an active ingredient in anti aging skincare products. When delivered into the skin nanotechnology, the apple stem cells provide more dramatic results in decreasing lines, wrinkles, and environmental damage.
Currently referred to as The Fountain of Youth, intense research has proved that with just a concentration level of 0.1 % of the PhytoCellTec (apple stem cell extract) could proliferate a wealth of human stem cells by an astounding 80%! These wonder cells work super efficiently and are completely safe. Of the numerous benefits of apple stems cells, the most predominant include:
Skin Layers
Skin Cell Activity Before
Skin Cell Activity After 1 Hour
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Apple Stem Cells - Sonya Dakar Skin Clinic
Stem Cell Therapy for Heart Disease – Cleveland Clinic
By LizaAVILA
Stem Cell Therapy: Helping the Body Heal Itself
Stem cells are natures own transformers. When the body is injured, stem cells travel the scene of the accident. Some come from the bone marrow, a modest number of others, from the heart itself. Additionally, theyre not all the same. There, they may help heal damaged tissue. They do this by secreting local hormones to rescue damaged heart cells and occasionally turning into heart muscle cells themselves. Stem cells do a fairly good job. But they could do better for some reason, the heart stops signaling for heart cells after only a week or so after the damage has occurred, leaving the repair job mostly undone. The partially repaired tissue becomes a burden to the heart, forcing it to work harder and less efficiently, leading to heart failure.
Initial research used a patients own stem cells, derived from the bone marrow, mainly because they were readily available and had worked in animal studies. Careful study revealed only a very modest benefit, so researchers have moved on to evaluate more promising approaches, including:
No matter what you may read, stem cell therapy for damaged hearts has yet to be proven fully safe and beneficial. It is important to know that many patients are not receiving the most current and optimal therapies available for their heart failure. If you have heart failure, and wondering about treatment options, an evaluation or a second opinion at a Center of Excellence can be worthwhile.
Randomized clinical trials evaluating these different approaches typically allow enrollment of only a few patients from each hospital, and hence what may be available at the Cleveland Clinic varies from time to time. To inquire about current trials, please call 866-289-6911 and speak to our Resource Nurses.
Cleveland Clinic is a large referral center for advanced heart disease and heart failure we offer a wide range of therapies including medications, devices and surgery. Patients will be evaluated for the treatments that best address their condition. Whether patients meet the criteria for stem cell therapy or not, they will be offered the most advanced array of treatment options.
Allogenic: from one person to another (for example: organ transplant)
Autogenic: use of one's own tissue
Myoblasts: immature muscle cells, may be able to change into functioning heart muscle cells
Stem Cells: cells that have the ability to reproduce, generate new cells, and send signals to promote healing
Transgenic: Use of tissue from another species. (for example: some heart valves from porcine or bovine tissue)
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Stem Cell Therapy for Heart Disease - Cleveland Clinic
Bone marrow (stem cell) transplant and donation
By LizaAVILA
A transplant of the stem cells that form in bone marrow can help people recover from certain types of cancers and blood and bone marrow disorders, but having a bone marrow or stem cell transplant can require a donation from someone.
The bones of the body are hollow and in the centre especially in the flat bones such as the breastbone and pelvis can be found a soft tissue known as bone marrow. This sponge-like substance produces stem cells. These are immature cells that constantly divide to produce new cells, some of which grow into mature blood cells used by the body. These include:
Stem cells need to divide rapidly to make millions of blood cells every day. Without these stem cells it would be impossible to survive.
People who have a condition that damages bone marrow may not have enough stem cells to produce normal blood cells. This can occur if there is a type of bone marrow failure or a genetic blood or immune system disorder.
In other cases, treating people with certain types of cancer sometimes requires giving very high doses of chemotherapy to kill the cancer cells in the body. Whole body radiotherapy may also be used to kill off the cancer cells. However, these treatments can also kill healthy cells in the body, including the stem cells in bone marrow.
People who may need a bone marrow transplant include those with:
The collected stem cells are added to a solution that is put into the body by using a drip, similar to receiving a blood transfusion. These cells enter the bloodstream and then travel to the bones, where they can start producing blood cells again. In people who have cancer, this is performed the day after treatment with chemotherapy or radiotherapy ends.
Because having a transplant involves being given different medicines and blood transfusions as well as the transplant itself, the patient may be given a central line, or central venous catheter. An operation will be performed to insert a thin tube through the skin near the collarbone and into a large vein near the heart.
The transplant itself isn't painful, but the person will need to remain in hospital for between 5 to 6 weeks while their bone marrow recovers, allowing time for the donated stem cells to settle in and start producing new cells. Antibiotics are often given to limit the risk of infection, which is particularly high during this period and the reason why the person may be placed in isolation. Blood transfusions may also be necessary until the bone marrow is making enough new blood cells. The person will also be monitored to ensure the stem cells have been accepted.
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Bone marrow (stem cell) transplant and donation
Skin Stem Cells: Benefits, Types, Medical Applications and …
By LizaAVILA
Our skin has the amazing capability to renew itself throughout our adult life. Also, our hair follicle goes through a cycle of growth and degeneration. This happens all the time in our skin even though we are not aware of it. However, even though skin renews itself we still have to help it a little bit to get better results. Stem cells play an important role in this process of skin renewal or hair growth and the purpose of this article is to discuss and provide additional information about these tiny cells that play a big part in our life.
Skin stem cell is defined as multipotent adult skin cells which are able to self-renew or differentiate into various cell lineages of the skin. These cells are active throughout our life via skin renewal process or during skin repair after injuries. These cells reside in the epidermis and hair follicle and one of their purposes is to ensure the maintenance of adult skin and hair regeneration.
The truth is, without these little cells, our skin wouldnt be able to cope with various environmental influences. Our skin is exposed to different influences 24/7, for example, washing your face with soap, going out during summer or cold winter days etc. All these factors have a big impact on our skin and it constantly has to renew itself to stay in a good condition. This is where skin stem cells step in. They make sure your skin survives the influence of constant stress, heat, cold, even makeup, soap, etc.
Our skin is quite sensitive and due to its constant exposure to different influences throughout the day, it can get easily damage. Damage to skin cells can be caused by pretty much everything, from soap to cigarette smoke. One of the most frequent skin cell damages are the result of:
Skin stem cells are still subjected to scientific projects where researchers are trying to discover as much as possible about them. So far, they have identified several types of these cells, and they are:
Also, some scientists suggest that there is another type of stem cells mesenchymal stem cells which can be found in dermis (layer situated below the epidermis) and hypodermis (innermost and the thickest layer of the skin). However, this claim has been branded controversial and is a subject of many arguments and disputes between scientists. It is needed to conduct more experiments to find out whether this statement really is true.
Stem cells are found in many organs and tissues, besides skin. For example, scientists have discovered stem sells in brain, heart, bone marrow, peripheral blood, skeletal muscle, teeth, liver, gut etc. Stem cells reside in a specific area of each tissue or organ and that area is called stem cell niche. The same case is with the skin as well.
The ability of stem cells to regenerate and form almost any cell type in the body inspired scientists to work on various skin products that contain stem cells. Also, they decided to investigate the effect of plant stem cells on human skin. They discovered that plant stem cells are, actually, very similar to human skin stem cells and they function in a similar way as well. This discovery made scientists turn to plants as the source of stem cells and are trying to include them into the skin products due to their effectiveness in supporting skins cellular turnover. Another similarity between plant stem cells and human skin stem cells is their ability to develop according to their environment.
Fun Fact: The inspiration to use plant stem cells in skin care came from an unusual place almost extinct apple tree from Switzerland.
The benefits of plant stem cells on human skin are versatile. They offer possibility to treat some skin conditions, heal wounds, and repair the skin after some injury faster than it would usually take. Also, they bring back elasticity to the skin, reduce the appearance of wrinkles and slow down the aging process.
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Skin Stem Cells: Benefits, Types, Medical Applications and ...
Clinical GMP-grade iPS cell production – Stem Cell Assays
By LizaAVILA
Recently, Ive written about transition from iPS cell research to iPS cell large-scale manufacturing and automation. Ive described iPS cell process development in Cellular Dynamics International and New York Stem Cell Foundation Research Institute. Today, Id like to share presentations of 2 more players in the field Lonza and Roslin Cells. Both presentations were recorded at Stem Cell Meeting on the Mesa, held on October 14-16, 2013.
What was especially interesting to see a cost comparison between research and clinical-grade GMP-produced iPS cell lines:
(Screenshot from Lonza presentation at Stem Cell Meeting on the Mesa, 2013)
Interestingly, the major cost contributor in GMP-grade iPS cell production is a facility cost. I think, this is a first estimation of cost difference, presented for public.
The framework for establishing clinical-grade iPS cell manufacturing, nicely outlined in the recent article. Id also recommend you to read the following open access articles:
Tagged as: cost, iPS, manufacturing
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Clinical GMP-grade iPS cell production - Stem Cell Assays
Stem cell controversy – Wikipedia, the free encyclopedia
By LizaAVILA
The stem cell controversy is the consideration of the ethics of research involving the development, usage, and destruction of human embryos. Most commonly, this controversy focuses on embryonic stem cells. Not all stem cell research involves the creation, usage and destruction of human embryos. For example, adult stem cells, amniotic stem cells and induced pluripotent stem cells do not involve creating, using or destroying human embryos and thus are minimally, if at all, controversial.
The use of stem cells has been happening for decades. In 1998, scientists discovered how to extract stem cells from human embryos. This discovery led to moral ethics questions concerning research involving embryo cells, such as what restrictions should be made on studies using these types of cells? At what point does one consider life to begin? Is it just to destroy an embryo cell if it has the potential to cure countless numbers of patients? Political leaders are debating how to regulate and fund research studies that involve the techniques used to remove the embryo cells. No clear consensus has emerged. Other recent discoveries may extinguish the need for embryonic stem cells.[1]
Since stem cells have the ability to differentiate into any type of cell, they offer something in the development of medical treatments for a wide range of conditions. Treatments that have been proposed include treatment for physical trauma, degenerative conditions, and genetic diseases (in combination with gene therapy). Yet further treatments using stem cells could potentially be developed thanks to their ability to repair extensive tissue damage.[2]
Great levels of success and potential have been shown from research using adult stem cells. In early 2009, the FDA approved the first human clinical trials using embryonic stem cells. Embryonic stem cells can become all cell types of the body which is called totipotent. Adult stem cells are generally limited to differentiating into different cell types of their tissue of origin. However, some evidence suggests that adult stem cell plasticity may exist, increasing the number of cell types a given adult stem cell can become. In addition, embryonic stem cells are considered more useful for nervous system therapies, because researchers have struggled to identify and isolate neural progenitors from adult tissues[citation needed]. Embryonic stem cells, however, might be rejected by the immune system - a problem which wouldn't occur if the patient received his or her own stem cells.
Some stem cell researchers are working to develop techniques of isolating stem cells that are as potent as embryonic stem cells, but do not require a human embryo.
Some believe that human skin cells can be coaxed to "de-differentiate" and revert to an embryonic state. Researchers at Harvard University, led by Kevin Eggan, have attempted to transfer the nucleus of a somatic cell into an existing embryonic stem cell, thus creating a new stem cell line.[3] Another study published in August 2006 also indicates that differentiated cells can be reprogrammed to an embryonic-like state by introducing four specific factors, resulting in induced pluripotent stem cells.[4]
Researchers at Advanced Cell Technology, led by Robert Lanza, reported the successful derivation of a stem cell line using a process similar to preimplantation genetic diagnosis, in which a single blastomere is extracted from a blastocyst.[5] At the 2007 meeting of the International Society for Stem Cell Research (ISSCR),[6] Lanza announced that his team had succeeded in producing three new stem cell lines without destroying the parent embryos. "These are the first human embryonic cell lines in existence that didn't result from the destruction of an embryo." Lanza is currently in discussions with the National Institutes of Health (NIH) to determine whether the new technique sidesteps U.S. restrictions on federal funding for ES cell research.[7]
Anthony Atala of Wake Forest University says that the fluid surrounding the fetus has been found to contain stem cells that, when utilized correctly, "can be differentiated towards cell types such as fat, bone, muscle, blood vessel, nerve and liver cells". The extraction of this fluid is not thought to harm the fetus in any way. He hopes "that these cells will provide a valuable resource for tissue repair and for engineered organs as well".[8]
The status of the human embryo and human embryonic stem cell research is a controversial issue as, with the present state of technology, the creation of a human embryonic stem cell line requires the destruction of a human embryo. Stem cell debates have motivated and reinvigorated the pro-life movement, whose members are concerned with the rights and status of the embryo as an early-aged human life. They believe that embryonic stem cell research instrumentalizes and violates the sanctity of life and is tantamount to murder.[9] The fundamental assertion of those who oppose embryonic stem cell research is the belief that human life is inviolable, combined with the belief that human life begins when a sperm cell fertilizes an egg cell to form a single cell.
A portion of stem cell researchers use embryos that were created but not used in in vitro fertility treatments to derive new stem cell lines. Most of these embryos are to be destroyed, or stored for long periods of time, long past their viable storage life. In the United States alone, there have been estimates of at least 400,000 such embryos.[10] This has led some opponents of abortion, such as Senator Orrin Hatch, to support human embryonic stem cell research.[11] See Also Embryo donation.
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Stem cell controversy - Wikipedia, the free encyclopedia
Cancer Center: Types, Symptoms, Causes, Tests, and …
By LizaAVILA
Understanding Cancer -- Diagnosis and Treatment How Is Cancer Diagnosed?
The earlier cancer is diagnosed and treated, the better the chance of its being cured. Some types of cancer -- such as those of the skin, breast, mouth, testicles, prostate, and rectum -- may be detected by routine self-exam or other screening measures before the symptoms become serious. Most cases of cancer are detected and diagnosed after a tumor can be felt or when other symptoms develop. In a few cases, cancer is diagnosed incidentally as a result of evaluating or treating other medical conditions.
Cancer diagnosis begins with a thorough physical exam and a complete medical history. Laboratory studies of blood, urine, and stool can detect abnormalities that may indicate cancer. When a tumor is suspected, imaging tests such as X-rays, computed tomography (CT), magnetic resonance imaging (MRI), ultrasound, and fiber-optic endoscopy examinations help doctors determine the cancer's location and size. To confirm the diagnosis of most cancers , a biopsy needs to be performed in which a tissue sample is removed from the suspected tumor and studied under a microscope to check for cancer cells.
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Cancer Center: Types, Symptoms, Causes, Tests, and ...
Mesenchymal stem cells in the treatment of spinal cord …
By LizaAVILA
World J Stem Cells. 2014 Apr 26; 6(2): 120133.
Venkata Ramesh Dasari, Krishna Kumar Veeravalli, Department of Cancer Biology and Pharmacology, University of Illinois College of Medicine at Peoria, Peoria, IL 61656, United States
Dzung H Dinh, Department of Neurosurgery and Illinois Neurological Institute, University of Illinois College of Medicine at Peoria, Peoria, IL 61656, United States
Correspondence to: Dzung H Dinh, MD, Department of Neurosurgery and Illinois Neurological Institute, University of Illinois College of Medicine at Peoria, One Illini Drive, Peoria, IL 61605, United States. ude.ciu@hnidd
Telephone: +1- 309-6552642 Fax: +1-309-6713442
Received 2013 Oct 30; Revised 2014 Feb 19; Accepted 2014 Mar 11.
With technological advances in basic research, the intricate mechanism of secondary delayed spinal cord injury (SCI) continues to unravel at a rapid pace. However, despite our deeper understanding of the molecular changes occurring after initial insult to the spinal cord, the cure for paralysis remains elusive. Current treatment of SCI is limited to early administration of high dose steroids to mitigate the harmful effect of cord edema that occurs after SCI and to reduce the cascade of secondary delayed SCI. Recent evident-based clinical studies have cast doubt on the clinical benefit of steroids in SCI and intense focus on stem cell-based therapy has yielded some encouraging results. An array of mesenchymal stem cells (MSCs) from various sources with novel and promising strategies are being developed to improve function after SCI. In this review, we briefly discuss the pathophysiology of spinal cord injuries and characteristics and the potential sources of MSCs that can be used in the treatment of SCI. We will discuss the progress of MSCs application in research, focusing on the neuroprotective properties of MSCs. Finally, we will discuss the results from preclinical and clinical trials involving stem cell-based therapy in SCI.
Keywords: Spinal cord injury, Mesenchymal stem cells, Bone marrow stromal cells, Umbilical cord derived mesenchymal stem cells, Adipose tissue derived mesenchymal stem cells
Core tip: Despite our deeper understanding of the molecular changes that occurs after the spinal cord injury (SCI), the cure for paralysis remains elusive. In this review, the pathophysiology of SCI and characteristics and potential sources of mesenchymal stem cells (MSCs) that can be used in the treatment of SCI were discussed. We also discussed the progress of application of MSCs in research focusing on the neuroprotective properties of MSCs. Finally, we discussed the results from preclinical and clinical trials involving stem cell-based therapy in SCI.
Traumatic spinal cord injury (SCI) continues to be a devastating injury to affected individuals and their families and exacts an enormous financial, psychological and emotional cost to them and to society. Despite years of research, the cure for paralysis remains elusive and current treatment is limited to early administration of high dose steroids and acute surgical intervention to minimize cord edema and the subsequent cascade of secondary delayed injury[1-3]. Recent advances in neurosciences and regenerative medicine have drawn attention to novel research methodologies for the treatment of SCI. In this review, we present our current understanding of spinal cord injury pathophysiology and the application of mesenchymal stem cells (MSCs) in the treatment of SCI. This review will be more useful for basic and clinical investigators in academia, industry and regulatory agencies as well as allied health professionals who are involved in stem cell research.
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cardiovascular disease :: Cardiac stem cells | Britannica.com
By LizaAVILA
Cardiac stem cells, which have the ability to differentiate (specialize) into mature heart cells and therefore could be used to repair damaged or diseased heart tissue, have garnered significant interest in the development of treatments for heart disease and cardiac defects. Cardiac stem cells can be derived from mature cardiomyocytes through the process of dedifferentiation, in which mature heart cells are stimulated to revert to a stem cell state. The stem cells can then be stimulated to redifferentiate into myocytes or endothelial cells. This approach enables millions of cardiac stem cells to be produced in the laboratory.
In 2009 a team of doctors at Cedars-Sinai Heart Institute in Los Angeles, California, reported the first attempted use of cardiac stem cell transplantation to repair damaged heart tissue. The team removed a small section of tissue from the heart of a patient who had suffered a heart attack, and the tissue was cultured in a laboratory. Cells that had been stimulated to dedifferentiate were then used to produce millions of cardiac stem cells, which were later reinfused directly into the heart of the patient through a catheter in a coronary artery. A similar approach was used in a subsequent clinical trial reported in 2011; this trial involved 14 patients suffering from heart failure who were scheduled to undergo cardiac bypass surgery. More than three months after treatment, there was slight but detectable improvement over cardiac bypass surgery alone in left ventricle ejection fraction (the percentage of the left ventricular volume of blood that is ejected from the heart with each ventricular contraction).
Stem cells derived from bone marrow, the collection of which is considerably less invasive than heart surgery, are also of interest in the development of regenerative heart therapies. The collection and reinfusion into the heart of bone marrow-derived stem cells within hours of a heart attack may limit the amount of damage incurred by the muscle.
There are many types of arterial diseases. Some are generalized and affect arteries throughout the body, though often there is variation in the degree they are affected. Others are localized. These diseases are frequently divided into those that result in arterial occlusion (blockage) and those that are nonocclusive in their manifestations.
Atherosclerosis, the most common form of arteriosclerosis, is a disease found in large and medium-sized arteries. It is characterized by the deposition of fatty substances, such as cholesterol, in the innermost layer of the artery (the intima). As the fat deposits become larger, inflammatory white blood cells called macrophages try to remove the lipid deposition from the wall of the artery. However, lipid-filled macrophages, called foam cells, grow increasingly inefficient at lipid removal and undergo cell death, accumulating at the site of lipid deposition. As these focal lipid deposits grow larger, they become known as atherosclerotic plaques and may be of variable distribution and thickness. Under most conditions the incorporation of cholesterol-rich lipoproteins is the predominant factor in determining whether or not plaques progressively develop. The endothelial injury that results (or that may occur independently) leads to the involvement of two cell types that circulate in the bloodplatelets and monocytes (a type of white blood cell). Platelets adhere to areas of endothelial injury and to themselves. They trap fibrinogen, a plasma protein, leading to the development of platelet-fibrinogen thrombi. Platelets deposit pro-inflammatory factors, called chemokines, on the vessel walls. Observations of infants and young children suggest that atherosclerosis can begin at an early age as streaks of fat deposition (fatty streaks).
Atherosclerotic lesions are frequently found in the aorta and in large aortic branches. They are also prevalent in the coronary arteries, where they cause coronary artery disease. The distribution of lesions is concentrated in points where arterial flow gives rise to abnormal shear stress or turbulence, such as at branch points in vessels. In general the distribution in most arteries tends to be closer to the origin of the vessel, with lesions found less frequently in more distal sites. Hemodynamic forces are particularly important in the system of coronary arteries, where there are unique pressure relationships. The flow of blood through the coronary system into the heart muscle takes place during the phase of ventricular relaxation (diastole) and virtually not at all during the phase of ventricular contraction (systole). During systole the external pressure on coronary arterioles is such that blood cannot flow forward. The external pressure exerted by the contracting myocardium on coronary arteries also influences the distribution of atheromatous obstructive lesions.
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cardiovascular disease :: Cardiac stem cells | Britannica.com
StemCells, Inc. Announces Commencement of the Second …
By LizaAVILA
NEWARK, Calif., Jun 04, 2015 (GLOBE NEWSWIRE via COMTEX) --
StemCells, Inc. STEM, +0.00% a world leader in the research and development of cell-based therapeutics for the treatment of central nervous system diseases and disorders, announced today that it has enrolled its first subject in Cohort 2 of its Phase II Pathway Study. The study is designed to assess the efficacy of the Company's proprietary HuCNS-SC platform technology (purified human neural stem cells) for the treatment of cervical spinal cord injury. Cohort 2 will enroll 40 patients and forms the single-blinded controlled arm of the Phase II study. The primary efficacy outcome being tested in Cohort 2 is the change in motor strength of the various muscle groups in the upper extremities innervated by the cervical spinal cord.
The Pathway Study is the first clinical trial designed to evaluate both the safety and efficacy of human neural stem cells transplanted into the spinal cord of patients with cervical spinal cord injury. Traumatic injuries to the neck can damage the cervical spinal cord and result in impaired sensation and motor function of the arms, legs, and trunk, also referred to as quadriplegia. The trial has 3 cohorts. The primary Cohort is Cohort 2 which is being conducted as a randomized, controlled, single-blind Cohort and efficacy will be primarily measured by assessing motor function according to the International Standards for Neurological Classification of Spinal Cord Injury (ISNCSCI). The trial will follow the participants for one year and will enroll up to 52 subjects.
Cohort 1 of the Pathway Study is an open-label, HuCNS-SC dose-escalation arm involving six patients. Safety data from all six subjects was reviewed by an independent Data Monitoring Committee and approval was provided to commence with Cohort 2. No safety or tolerability issues were seen at any of the dosing levels. The six-month outcome from Cohort 1 will be disclosed as interim data later this year.
Cohort 3 is an optional open label Cohort targeted to enroll 6 patients. This Cohort is designed to assess safety and preliminary efficacy in patients with less severe injuries (AIS C).
"The initiation of Cohort 2 begins the next phase of our clinical efforts towards a potential breakthrough therapy for spinal cord injury," said Stephen Huhn, M.D., FACS, FAAP, Vice President, Clinical Research and Chief Medical Officer at StemCells, Inc. "This is the first blinded, controlled clinical trial to be conducted using human neural stem cells. The goal of this proof-of-concept study is to demonstrate the potential efficacy of our cells as a treatment for victims of spinal cord injury. We currently have seven sites enrolling patients and expect to reach a total of fourteen active North American sites by year end. Conducting a multi-center study on this scale should allow us to efficiently enroll the study."
The Company completed enrollment and dosing in its open-label Phase I/II study in thoracic spinal cord injury in April 2014 and has reported top-line results. Sustained post-transplant gains in sensory function were demonstrated in seven of the twelve patients. Two patients in the Phase I/II study converted from a complete injury (AIS A) to an incomplete injury (AIS B). The final results also continue to confirm the favorable safety profile of the cells and the surgical procedure.
About the Pathway Cervical Spinal Cord Injury Clinical Trial
The Company's Phase II Pathway Study, titled "Study of Human Central Nervous System (CNS) Stem Cell Transplantation in Cervical Spinal Cord Injury," will evaluate the safety and efficacy of transplanting the Company's proprietary human neural stem cells (HuCNS-SC cells), into patients with traumatic injury in the cervical region of the spinal cord. Conducted as a randomized, controlled, single-blind study, the trial will measure efficacy by assessing motor function according to the International Standards for Neurological Classification of Spinal Cord Injury (ISNCSCI). The primary efficacy outcome will focus on change in upper extremity strength. The trial will enroll approximately 52 subjects and follow the patients for 12 months post-transplant. The first cohort of six patients completed enrollment in April and was designed to establish the cell dose for onward testing in the second cohort of the study.
Information about the Company's spinal cord injury program can be found on the StemCells, Inc. website at:
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StemCells, Inc. Announces Commencement of the Second ...