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Exciting Strides Being Made in Stem Cell Research

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    Exciting Strides Being Made in Stem Cell Research

    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
    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.
    "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 ( 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.

    SOURCE American Society of Hematology
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