2009-03-31
(WASHINGTON) - For the first time, scientists have
shown that amniotic fluid (the protective liquid surrounding an embryo)
may be a potential new source of hematopoietic stem cells for
therapeutic applications. The study was prepublished online on February
12, 2009, in Blood, the official journal of the American Society of Hematology.
“Building on observations made by other scientists, our research
team wondered whether hematopoietic stem cells could be detected in
amniotic fluid. We looked at the capacity of these cells to form new
blood cells both inside and outside the body, and also compared their
characteristics to other well-known sources of stem cells,” said senior
study author Marina Cavazzana-Calvo, MD, PhD, of INSERM, the national
French institute for health and biomedical research. Isabelle
André-Schmutz, PhD, of INSERM, also a senior author of the study,
added, “The answer was a resounding ‘yes’ – the cells we isolated from
the amniotic fluid are a new source of stem cells that may potentially
be used to treat a variety of human diseases.”
To conduct the study, amniotic fluid was collected from pregnant
mice between 9.5 and 19.5 days post-coitus. Human amniotic fluid was
collected during routine diagnostic procedures (amniocentesis) from
volunteer donors between seven and 35 weeks of pregnancy.
Amniotic fluid (AF) cells that had markers similar to bone marrow
stem cells (termed AFKL cells) were then isolated for use in
experiments, as these cell markers were indicative of progenitor cells
(cells that have the capacity to differentiate into other types of
cells).
In vitro, AFKL cells from both mice and humans were able to
generate all blood cell lineages, including red (erythroid) blood cells
and white (myeloid and lymphoid) blood cells in experiments performed
outside the animals. But the scientists also wanted to explore the AFKL
cells’ hematopoietic (blood-forming) potential in vivo.
Therefore, adult mice were irradiated to destroy their capacity to
produce blood cells and injected with either AFKL cells or fetal liver
cells. Fetal liver was used for comparison as it is the primary source
for hematopoietic cells in developing embryos.
The peripheral blood of the transplanted mice was examined every
four weeks, and after 16-18 weeks the blood-forming organs (bone
marrow, spleen, thymus, and lymph nodes) of the mice were dissected.
Transplants using mouse AFKL cells were found to be successful; newly
formed white blood cells of all lineages derived from AFKL cells
appeared in most of the irradiated mice four weeks after the procedure.
As expected, all of these blood cell types were detected in all of the
control group mice who received fetal liver cell transplants.
Scientists continued to find AFKL-derived cells in the irradiated mice
four months later, demonstrating the long-term ability of the
transplanted cells to produce new blood cells.
Bone marrow samples from the transplanted mice were also taken and
injected in a second set of mice and the peripheral blood of this new
group of irradiated mice was analyzed and their hematopoietic organs
examined after 10-13 weeks. The secondary transplants with mouse AFKL
cells were partially successful with some of the mice engrafting the
donor cells. This finding shows that AFKL cells have the ability to
self-renew, a key characteristic of stem cells.
Though the human AFKL cells failed to reconstitute the hematopoietic
system in irradiated, immunodeficient mice, experiments are currently
underway to overcome obstacles that may have led to this failure, such
as using a low number of cells for the injection and conducting the
transplant in adult mice (engraftment is easier to obtain in newborn
mice).
As additional confirmation of the probability that AFKL cells are
indeed stem cells, the researchers examined them for the expression of
specific genes known to be involved in hematopoietic development. The
overall gene expression profile of the AFKL cells was found to resemble
blood cell progenitors from known hematopoiesis sites such as the
aorta-gonadmesonephros region, placenta, and the umbilical/vitelline
arteries.
Reporters who wish to receive a copy of the study or arrange an
interview with senior authors Drs. Cavazzana-Calvo and André-Schmutz,
may contact Patrick C. Irelan at 202-776-0544 or pirelan@hematology.org.
The American Society of Hematology (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. In September 2008, ASH launched Blood: The Vital Connection (www.bloodthevitalconnection.org),
a credible online resource addressing bleeding and clotting disorders,
anemia, and cancer. It provides hematologist-approved information about
these common blood conditions including risk factors, preventive
measures, and treatment options.
Blood, the official journal of ASH, is the most cited peer-reviewed publication in the field. Blood is issued to Society members and other subscribers weekly and is available in print and online at www.bloodjournal.org.
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