Skip to comments.Exciting Strides Being Made in Stem Cell Research (Adult stem cells)
Posted on 12/13/2005 10:15:11 AM PST by DaveLoneRanger
ATLANTA, Dec. 12 /PRNewswire/ -- Four studies presented today at the 47th Annual Meeting of the American Society of Hematology highlight new information about the potential of stem cells, from determining the type and location of stem cells in bone marrow to controlling the differentiation of cells into desired cell types and determining how well stem cell transplants actually work in treating cancers.
Stem cells are unspecialized cells with two unique characteristics: the capacity to multiply and renew themselves for long periods of time, and under certain conditions, the ability to differentiate into different kinds of cells -- liver, brain, skin, and so forth -- needed in human development. Both qualities make stem cells, at least theoretically, a key tool in regenerative and reparative medicine.
"Research is unlocking the secrets of the stem cell, answering some questions and posing others. We are finding out there are more types of stem cells than we previously thought and are even comparing the effectiveness of stem cells from different sources in treating leukemia," said Stephen G. Emerson, M.D., Ph.D., University of Pennsylvania Cancer Center, Philadelphia, Penn. "ASH enthusiastically supports all avenues of stem cell research and has an enduring commitment to move the science forward to help patients."
Evidence That Neural Tissue-Committed Stem Cells (NTCSC) Reside in the Human Bone Marrow and are Mobilized Into Peripheral Blood in a Patient After Stroke [Abstract 392]
Researchers have found for the first time that adult bone marrow contains a distinct population of non-hematopoietic stem cells that are uniquely responsible for the development of nerve tissue. Roaming in the bloodstream, these neural tissue committed stem cells (TCSCs), also known as very small embryonic-like (VSEL) stem cells, are mobilized by a stroke and provide immediate first aid to damaged nerve tissue, according to a study led by researchers from the James Graham Brown Cancer Center, University of Louisville, Louisville, Ky.
Hematopoietic stem cells (HSCs) in bone marrow had been thought to be the only source of cells that could differentiate into blood and other kinds of tissue. This study provides the first evidence that bone marrow not only contains a mixed population of cells, but that the non-hematopoietic stem cells are the only cells capable of developing (or differentiating) into all types of neural tissue and contributing to brain repair.
The findings will help researchers refine their thinking about how the body repairs nerve and brain tissue throughout the life cycle. "We observed that the number of neural tissue committed stem cells decreases with age, which may explain why the brain regeneration process becomes less effective in older individuals," said Magdalena Kucia, Ph.D., Stem Cell Biology Program, James Graham Brown Cancer Center.
Researchers studied 14 patients with stroke and found an increase in the bloodstream of cells expressing neural TCSCs after the stroke. The maximum elevation of these cells occurred within 24 to 72 hours after a stroke and remained elevated up to one week. The degree of mobilization of these cells correlated with younger age, smaller size of the stroke, and less extensive stroke.
These new findings in humans are based on research performed on mice. Earlier mice experiments have shown that neural TCSCs circulate in low numbers in the bloodstream under normal conditions and that their levels increase during the murine model of stroke. Investigators took both the HSCs and the non-hematopoietic cells from mice bone marrow, and found that only the latter were able to differentiate into cells that were precursors to nerve cells.
The discovery of a stem cell that does not have to be cloned from human embryos could have vast implications for the future of medical treatments. "We have both purified and identified at a single cell level an adult counterpart of embryonic stem cells that is present in adult bone marrow. These cells are a real alternative to embryonic stem cells for obtaining a population of histocompatible, pluripotent stem cells for regeneration purposes," said Mariusz Ratajczak, M.D., Ph.D., University of Louisville, Louisville, Ky. "This population of stem cells may be deposited in bone marrow early during development."
Recently, Dr. Ratajczak's team was able to establish culture conditions in vitro in which VSEL stem cells formed embryonic-like bodies that, in turn, may differentiate into neurons, macroglia, cardiomyocytes, and pancreatic cells. The identification of these cells and their successful expansion in the form of embryoid bodies may lead to the development of new therapeutic strategies that will avoid the use of human embryos.
Human Embryonic Stem Cells Differentiate into Functional Natural Killer Cells With the Capacity to Mediate Anti-Tumor Activity [Abstract 763]
Researchers from the University of Minnesota have, for the first time, generated natural killer cells from human embryonic stem cells, a key step in understanding how to support the body's fight against cancers. Natural killer (NK) cells, part of the body's immune system, kill virus and tumor cells and are key to mediating the body's rejection reaction to blood transplants used in the treatment of myeloid leukemias.
"We are only beginning to learn how human embryonic stem cells (hESCs) differentiate and mature into myeloid (blood) and lymphoid cells," says Dan Kaufman, M.D., Ph.D., University of Minnesota, Minneapolis, Minn. "In this research, we have shown that hESCs can develop into lymphoid cells, specifically natural killer cells that are effective in targeting and destroying cancer cells."
Researchers used human embryonic hematopoietic (blood-producing) progenitor cells, stimulated with specific growth factors, to culture the killer cells. Development of mature NK cells took approximately 28 days. Proof that the cells were indeed killer cells came from testing for proteins unique to killer cells. The hESC-derived killer cells expressed receptors known to regulate their cytolytic (cell disintegration) ability, including killer lg-like receptors, C-type lectin-like receptors, and natural cytotoxicity receptors. They also expressed CD16, a protein that binds to antibodies and is usually expressed on more mature natural killer cells.
The cells not only looked like killer cells, but acted like them. The researchers found that the hESC-derived lymphoid cells targeted and killed human tumor cells through two distinct mechanisms. To see how the NK cells acted directly on cancer cells, the team tested them against K562 erythroleukemia and Raji B-lymphoblastoid cells. The former were killed directly by the cultured killer cells. As expected, the Raji cells were not destroyed directly by the killer cells; however, the killer cells were able to bind to the Raji cells and kill them when the cancer cells were treated with an antibody (anti-CD20) that attracted the NK cells.
In a second test of the NK cells' effectiveness, researchers were able to demonstrate the NKs' ability to increase the production of cytokines, such as interferon. Cytokines are proteins that regulate the body's immune response, in part by regulating the growth and differentiation of T-cells and B-cells.
Future research could lead to improvements in the treatment of leukemia. "For example, we may be able to develop hESC-derived killer cells that target specific types of leukemia cells. Or, we may develop killer cells matched -- and therefore deadly to -- a patient's particular tumor cells," said Dr. Kaufman.
"Our first challenge, however, is to scale up the growth of the hESC- derived cells to obtain enough cells for the next stage -- testing the effectiveness of the cells in killing tumors in mice, which may eventually lead to human testing."
Outcomes of Unrelated Cord Blood and Haploidentical Stem Cell Transplantation in Adults with Acute Leukemia [Abstract 301]
Umbilical cord blood is an effective alternative source of hematopoietic stem cells used in transplants in people with high-risk acute leukemia, according to researchers from Europe and Israel. Hematopoietic stem cells (HSCs) are immature cells that can develop into three types of blood cells: white blood cells, which fight infections; red blood cells, which carry oxygen; and platelets, which help the blood to clot. They are found in bone marrow and in umbilical cord and placenta blood. The goal of HSC transplants is to restore a cancer patient's stem cells that have been destroyed by chemotherapy or radiation.
"We have shown that cord blood transplantation has been an effective means of treating patients with acute leukemias, as well as other malignant and non- malignant diseases. This has led to similar cancer-free survival rates when compared to patients receiving bone marrow transplants," says Vanderson Rocha, M.D., Ph.D., Hopital Saint Louis, Paris, on behalf of the Eurocord-Netcord group. "Combined with some of the other advantages of cord blood transplants, our findings should encourage physicians to consider them for their patients lacking a matched sibling donor."
Cord blood stem cells are easier to collect than bone marrow stem cells and do not require a perfect donor-recipient match, giving patients a better chance to find a suitable donor. When a patient with leukemia needs an HSC transplant and has no sibling donor, three options are currently possible: a compatible unrelated bone marrow donor, an unrelated cord blood (not necessarily matched) donor, or an incompatible family donor, called haploidentical T-cell stem cell transplantation. In a retrospective analysis, researchers compared outcomes in 364 adults with acute leukemia [144 with acute lymphocytic leukemia (ALL) and 220 with acute myelogenous leukemia (AML)] who received HSC transplants from cord blood or haploidentical stem cells.
In both groups, umbilical cord recipients had delayed neutrophil recovery (slower rebuilding of their white blood cell count) and higher incidence of acute GVHD than did those receiving haploidentical transplants. For those with AML, relapse, transplant-related mortality, and leukemia-free survival rates were not statistically different after umbilical cord or bone marrow transplants. However for those with ALL, relapse rates were lower and leukemia-free survival rates were higher for those receiving the umbilical cord transplants. This study demonstrates that almost all patients who need an HSC transplant and lack a matched sibling donor can be treated with different strategies of transplantation.
Mesenchymal Stem Cells for Treatment of Severe Acute and Extensive Chronic Graft-Versus-Host-Disease [Abstract 143]
Treatment for leukemia and other blood disorders often involves the transplant of hematopoietic stem cells (HSCs) from a donor to replace the patient's damaged or cancer cells. For HSC transplants to succeed, the donated stem cells must engraft or implant within the recipient's bone marrow, where they will grow to provide a new source of blood and immune cells.
A major complication of this transplant is graft-versus-host-disease (GVHD), an immune reaction by the donor cells to the recipient's body. GVHD occurs when T-cells from the donor (the graft) identify cells in the patient's body (the host) as foreign and attack them. This complication can develop within a few weeks of the transplant (acute GVHD) or much later (chronic GVHD).
Researchers from the Karolinska Institutet, Stockholm, Sweden, looked at transplanting another kind of stem cell, mesenchymal stem cells (MSCs), as a means of treating GVHD. Mesenchymal stem cells are non-hematopoietic cells found in the bone marrow that are capable of both self-renewal and differentiation into bone, cartilage, muscle, and fat cells. MSCs are similar to hematopoietic stem cells in that they are very rare (about 1 in 100,000 bone marrow cells). In treating GVHD, a key characteristic of MSCs is their ability to inhibit the donor's T-cells (a kind of white blood cell) from attacking the patient's tissue.
In this study, 14 patients with acute GVHD and two patients with extensive chronic GVHD were treated with infusions of MSCs. Nine patients received one dose, six received two doses, and one patient received three doses. The median dose was 1.0 (range 0.4-9) x 10E6 cells/kg body weight of the recipient. No side effects were seen. Of the 24 donors, two were HLA-identical siblings, 12 were haploidentical, and 10 were third-party HLA-mismatched.
Among the 14 patients treated for severe acute GVHD, six had complete responses, four showed improvement, and one had stable disease. Nine survived between two months and up to three years after transplantation. Four patients developed extensive chronic GVHD. One patient transplanted for AML in relapse developed recurrent leukemia. Three of the patients were not evaluated, two due to early death and one due to short follow up. The two patients treated for extensive chronic GVHD had transient responses. One died of Epstein-Barr virus lymphoma.
"We believe that mesenchymal stem cells have immune-modulatory and tissue- repairing effects and may be used for treatment of severe GVHD," said Katarina LeBlanc, M.D., Ph.D., Karolinska Institutet. "Based on our results, we look forward to conducting a larger clinical trial that will confirm these results and lead to new treatment options for these patients."
The American Society of Hematology (http://www.hematology.org) is the world's largest professional society concerned with the causes and treatment of blood disorders. Its mission is to further the understanding, diagnosis, treatment, and prevention of disorders affecting blood, bone marrow, and the immunologic, hemostatic, and vascular systems, by promoting research, clinical care, education, training, and advocacy in hematology.
Umbilical cord blood is an effective alternative source of hematopoietic stem cells ... "
Funny how this Yahoo news story (on the FINANCIAL page??) buries the true significance of this story. Lousiville radio reports it the following way:
University of Louisville scientists say they have made a discovery that could "change the face" of stem-cell research. They says they've discovered cells in the adult body that act like embyronic stem cells. If confirmed, the breakthrough could reduce the calls for embryonic cells research. That issue has caused major political controversy. Researchers from the James Graham Brown Cancer Center made the announcement Monday at a hematology conference.
It appears that Volker Enzmann has done a lot of work in this field, although he doesn't seem to have a moral quarrel with embryonic stem cells.
Someone needs to have a stem cell research ping list. I keep finding these stories which support adult stem cells, bone marrow, cord and placenta matter which don't require butchering a baby, and it seems like someone should have a ping list about these things.
"Funny how this Yahoo news story...."
It's not a news story. PR Newswire (in the byline) publishes press releases, which are written by the featured organizations themselves.
The coolly logical side of the stem-cell debate (the side I prefer most of the time) has ALWAYS said there was much more potential in adult stem cell research than in embryonic stem cells. a) there is no chance of rejection and b) the various processes developed for stimulating a differentiated cell back into a stem cell could be stunningly fertile ground for research.
Stem-cell research at U of L 'major step'
Nerve-repair work offers hope for treating array of disorders
By Laura Ungar
The video is dramatic.
A laboratory rat unable to use its right front paw because of a spinal cord injury struggles to walk across a rope, loses its footing and falls.
Then a rat that had the same injury scurries across the rope without a problem, just weeks after an injection containing adult stem cells from a human nose that were transformed into nerve cells.
The rats are part of a line of groundbreaking research at the University of Louisville that could lead to treatments for spinal cord injuries, multiple sclerosis, Parkinson's disease and other nerve disorders.
The rat's improvement after the injection is the second major discovery in the past few months at UofL that promises progress without using embryonic stem cells.
In December, a research team at the James Graham Brown Cancer Center announced it had transformed stem cells from adult mice into brain, heart, nerve and pancreatic cells.
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