Stem cell transplant can grow new immune system in certain mice,
Stanford researchers find
STANFORD, Calif. - Researchers at the Stanford University School of
Medicine have taken a small but significant step, in mouse studies,
toward the goal of transplanting adult stem cells to create a new
immune system for people with autoimmune or genetic blood diseases.
The researchers found a way to transplant new blood-forming stem
cells into the bone marrow of mice, effectively replacing their
immune systems. Many aspects of the technique would need to be
adapted before it can be tested in humans, said Irving Weissman, MD,
a co-senior author of the study and director of the Stanford
Institute for Stem Cell Biology and Regenerative Medicine. The work
was done on a particular group of mice that are a poor mimic for the
human immune system. Still, Weissman suggested the remaining hurdles
could eventually be overcome.
When those barriers are surmounted, the benefits are potentially big.
The study will be published in the Nov. 23 issue of Science.
A person with an autoimmune disease such as multiple sclerosis has a
defective immune system in which immune cells attack the person's own
body. An immune system transplant, much like a liver or heart
transplant, would give the person a new system that might not attack
the body.
The way to get a new immune system is to transplant new blood-forming
stem cells into the bone marrow, where they generate all the cells of
the blood. But before transplanting new stem cells, the old ones
first must be removed, which is currently done by intensive
chemotherapy or radiation. Those processes eliminate the cells of the
bone marrow, but also damage other tissue and can cause lasting
effects including infertility, brain damage and an increased risk of
cancer. A treatment for M.S. at the expense of brain function is
hardly an ideal therapy.
Weissman and co-first author Deepta Bhattacharya, PhD, a postdoctoral
scholar in Weissman's lab, thought one way around this problem would
be to eliminate only the blood-forming stem cells without affecting
bone marrow cells or other tissues. They worked with Agnieszka
Czechowicz, first author and medical student, to accomplish that feat
by injecting the mice with molecules that latch on to specific
proteins on the surface of the blood-forming stem cells, effectively
destroying the cells. That technique eliminated the blood-forming
stem cells without otherwise harming the mice.
"It is essentially a surgical strike against the blood-forming stem
cells," said Weissman, the Virginia & D.K. Ludwig Professor for
Clinical Investigation in Cancer Research. When they transplanted new
blood-forming stem cells into the mice, those cells took up residence
in the bone marrow and established a new blood and immune system.
In a person with autoimmune disease, that new immune system would
likely no longer attack tissues of the body. Likewise, in people with
a genetic disorder such as sickle cell anemia, the new blood system
would not have the sickle-cell mutation, eliminating the cause of
disease. However, the barriers are still significant.
First, the researchers don't know whether the same molecule on human
blood-forming stem cells would be the right one to target with a
therapy. Also, the mice they used in the study lack a functioning
immune system. They'll need to get the therapy working in mice with a
normal immune system before they can begin testing the technique in
humans.
Although these steps will take time to overcome, Weissman said he
considered this work to be the beginning of research that could lead
to human studies.
###
Daniel Kraft, MD, a postdoctoral scholar, also contributed to this
work.
The work was funded by fellowships from the Stanford Medical Scholars
Program, the Cancer Research Institute and by the National Institutes
of Health.
Stanford University Medical Center integrates research, medical
education and patient care at its three institutions - Stanford
University School of Medicine, Stanford Hospital & Clinics and Lucile
Packard Children's Hospital at Stanford. For more information, please
visit the Web site of the medical center's Office of Communication &
Public Affairs at http://mednews.
Public release date: 22-Nov-2007
Contact: Amy Adams
amyadams@stanford.
650-723-3900
Stanford University Medical Center
http://www.eurekale
Stem cell hope for immune disease
Bone marrow stem cells are able to form new blood and immune cells
Common immune system disorders, such as multiple sclerosis and
arthritis, could one day be treatable with bone marrow transplants,
research suggests.
Currently, the procedure is reserved for life-threatening disorders
because chemotherapy or radiotherapy is needed before a transplant
can be done.
But a protein may do the same job without dangerous side-effects, a
mouse study published in Science suggests.
However, the technique is not yet ready for testing in humans.
Stem cell studies are an important avenue of research which hold
promise in terms of treatments for MS
Dr Laura Bell, MS Society
The purpose of a bone marrow transplant is to infuse the body with
healthy adult stem cells which are able to form fresh blood and
immune cells.
In order for the new blood-forming stem cells to take hold, the
faulty cells in the bone marrow must first be destroyed, but the
aggressive therapies used can cause severe side effects, such as
brain damage, increased risk of cancer or infertility.
A person with an autoimmune disease such as multiple sclerosis has a
defective immune system in which immune cells attack the person's own
body.
Treatment with a bone marrow transplant would give the patient an
immune system that might not attack the body, but this could only be
done if the technique was less dangerous.
Antibodies
A team from Stanford University in the US found that injecting mice
with antibodies which latch on to specific proteins on the surface of
blood-forming stem cells, destroyed the cells without harming the
mice.
Blood-forming stem cells transplanted into the mice were then able to
take up residence in the bone marrow and set up a new blood and
immune system.
However, the barriers are still significant, the researchers said, as
the work was done on a particular group of mice that are a poor mimic
for the human immune system.
And it remains to be seen whether the same molecule on human blood-
forming stem cells would be the right one to use.
"It is essentially a surgical strike against the blood-forming stem
cells," said study author Dr Irving Weissman, director of the
Stanford Institute for Stem Cell Biology and Regenerative Medicine.
He added that he believed the hurdles to translating the research
into humans could be overcome.
Dr Laura Bell, research communications officer at the MS Society,
said: "Stem cell studies are an important avenue of research which
hold promise in terms of treatments for MS.
"This early stage study is interesting and we look forward to seeing
how the work translates into studies in people with MS."
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StemCells subscribers may also be interested in these sites:
Children's Neurobiological Solutions
http://www.CNSfoundation.org/
Cord Blood Registry
http://www.CordBlood.com/at.cgi?a=150123
The CNS Healing Group
http://groups.yahoo.com/group/CNS_Healing
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