SEATTLE, May 2 /PRNewswire-USNewswire/ -- Cutting the umbilical cord
doesn't necessarily sever the physical link between mother and child. Many
cells pass back and forth between the mother and fetus during pregnancy and
can be detected in the tissues and organs of both even decades later. This
mixing of cells from two genetically distinct individuals is called
microchimerism. The phenomenon is the focus of an increasing number of
scientists who wonder what role these cells play in the body.
A potentially significant one, it turns out. Research implicates that
maternal and fetal microchimerism plays both adverse and beneficial roles
in some autoimmune diseases as well as the prevention of at least one
cancer. This double-edged sword in turn has opened new avenues of study of
the body's immune system and the possibility of developing new tests and
therapies.
Two of the world's leading researchers in microchimerism are J. Lee
Nelson, M.D., of Fred Hutchinson Cancer Research Center's Clinical Research
Division; and V.K. Gadi, M.D., Ph.D., assistant professor of medicine at
the University of Washington. Nelson also is a professor of medicine at the
University of Washington. Gadi is also a research associate in the
Hutchinson Center's Clinical Research Division.
In 2007, they were the first to report these potentially beneficial
effects of microchimerism:
-- In January, Nelson reported the first discovery that cells passed
from mother to child during pregnancy can differentiate into functioning
islet beta cells that produce insulin in the child. The same study also
found maternal DNA in greater amounts in the blood of children and young
adults with Type 1 diabetes than their healthy siblings and a control
group, implying that the cells may be attempting to repair damaged tissue.
There was no evidence that the mother's cells were attacking the child's
insulin cells and no evidence that the maternal cells were targets of an
immune response from the child's immune system. The findings could lead to
new approaches to treating Type 1 diabetes. For example, if maternal
microchimerism results in cells that make insulin, a mother's stem cells
might be harvested and used to treat her diabetic child. Such cells would
have a genetic edge over donated islet cells from a cadaver that are
usually completely genetically mismatched.
-- Last October, a research paper by Gadi and Nelson described findings
that suggest fetal cells that persist in a woman's body long after
pregnancy in some cases may reduce the woman's risk of breast cancer. The
scientists examined the blood of 82 women post-pregnancy, 35 of whom had
had breast cancer. They looked for male DNA in the blood, presuming it was
present due to a prior pregnancy with a male. Fetal microchimerism (FMc)
was found significantly more often in healthy women than women with a
history of breast cancer, 43 percent versus 14 percent respectively. The
scientists concluded that FMc may contribute to the reduction of breast
cancer based on the hypothesis that residual fetal cells may provide immune
surveillance of malignant cells in the mother. They caution that further
studies are needed to confirm the theory.
Microchimerism reveals its Jekyll and Hyde personality in the case of
autoimmune diseases. In the late 1990s, Nelson's group was the first to
investigate microchimerism in an autoimmune disease:
-- In 1996 Nelson's lab proposed that fetal microchimerism might in
part explain the female predilection to autoimmune disease and they
subsequently discovered elevated levels of fetal microchimerism in the
blood of women with scleroderma compared to healthy women. Subsequent
studies found fetal microchimerism in internal organs and in skin affected
by scleroderma.
-- In 1999 Nelson's group found that maternal microchimerism persists
into adult life in individuals who have normal immune systems. They
presumed this is due to engraftment with maternal stem cells. Stem cells
can become multiple different types of cells. Researchers wondered whether
maternal cells can become part of the cells that make up tissues.
Scientists found maternal cells in the hearts of infants who died from
heart block due to neonatal lupus and identified that most of the maternal
cells were cardiac myocytes (heart muscle cells). They theorized that the
maternal cells are the target of an immune attack.
-- On the other hand, women with rheumatoid arthritis often have their
disease improve or even disappear during pregnancy. A beneficial role of
fetal microchimerism was suggested by the research finding that elevated
levels of fetal microchimerism significantly correlated with
pregnancy-induced amelioration of rheumatoid arthritis.
The Nelson lab has expanded its study of microchimerism into the fields
of reproduction, HIV/AIDS and transplantation. For example, scientists are
investigating microchimerism in complications of pregnancy, especially
preeclampsia, a disorder characterized by high blood pressure in women in
their third trimester of pregnancy, and in recurrent pregnancy loss.
Nelson's group also is investigating maternal microchimerism in
patients with HIV and is looking at whether maternal microchimerism levels
correlate with whether there is progression or non-progression to AIDS.
Transplantation of stem cells to treat some cancers results in
chimerism. Graft-vs.-host disease occurs more often if the cell donor is a
woman with prior pregnancies. Tests of female donor cells found they
contained male microchimerism, consistent with the interpretation that
fetal microchimerism contributes to graft-vs.-host disease. In kidney,
pancreas and islet transplantation, Gadi, Nelson and collaborators tested
serial serum samples and found that donor-specific microchimerism detection
may become a useful non-invasive test for early rejection. This has led to
work by several other research groups to therapeutically exploit the
principles of naturally-acquired microchimerism in their selection of
donors for transplantation.
The discovery that a mother's cells can turn up in her adult progeny
and that fetal cells can occur in women who were once pregnant heralds the
emergence of microchimerism as an important new theme in biology.
At Fred Hutchinson Cancer Research Center, our interdisciplinary teams
of world-renowned scientists and humanitarians work together to prevent,
diagnose and treat cancer, HIV/AIDS and other diseases. Our researchers,
including three Nobel laureates, bring a relentless pursuit and passion for
health, knowledge and hope to their work and to the world. For more
information, please visit http://fhcrc.org.
This news release was issued on behalf of Newswise(TM). For more
information, visit http://www.newswise.com.
SOURCE Fred Hutchinson Cancer Research Center
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CONTACT:
CONTACTS: Dean Forbes of Fred Hutchinson
Cancer Research Center, +1-206-667-2896, dforbes@fhcrc.org
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