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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.



SOURCE American Society of Hematology
Web Site: http://www.hematology.org