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The fresher the better
09-24-2013
EDIT CONNECT
SHARING OPTIONS:
DURHAM, N.C.—Stem cells are being
lauded and explored in
multiple indications, one of them being multiple sclerosis (MS). Transplants of
mesenchymal stem cells (MSCs) are being tested
in mice in clinical trials,
though their potential in humans with MS is not fully known as yet. What is
known, and has been reported in a recent study
in STEM CELLS Translational Medicine, is that
adipose-derived stem
cells from older donors are proving less effective than cells from younger
donors.
MSCs are a promising therapy for MS because they travel to
areas of damage caused by the disease and release trophic (cell
growth)
factors, in addition to exerting neuroprotective and immunomodulatory effects
to inhibit T cell proliferation. MS-related clinical trials have
confirmed the
safety of this kind of therapy, but Bruce Bunnell, Ph.D., of Tulane
University's Center for Stem Cell Research and Regenerative Medicine, says
questions still remain as to the exact
mechanism by which MSCs provide this
benefit to MS patients.
"All of our data would indicate that the
[MSC] cells are
very good and very efficient at quieting the inflammatory component of the
disease," says Bunnell. "When we look at a molecular,
pathologic level, we see
that the myelin destruction caused by the disease is nowhere near what it was
prior to treatment [with the MSCs], or if we
treat with other cell types, or do
a mock treatment. So whatever is going on seems to be able to help preserve
myelin, and when we look at the markers
of disease-associated inflammation,
they seem to have dropped dramatically.
"So there's this
connection between the inflammation and immune
cell infiltration into the spinal cord that causes this immune-mediated
disruption of myelin. What we
think is happening is by quieting the
inflammatory component, you're reducing the amount of inflammatory cell
inflammation into the spinal cord, and
that results in a decrease in the amount
of myelin destruction."
Bunnell served as lead author
for this study, working
alongside a team of his colleagues in Tulane as they tested MSCs transplants in
mice. The team induced chronic experimental
autoimmune encephalomyelitis in
mouse models, a disease similar to MS, and treated them before the onset of the
disease with human adipose-derived MSCs
derived from donors who were either
younger than 35 years of age or older than 60 years of age. Their results showed
that the transplants provided by
older donors are less effective and that the
older MSCs might actually increase the proliferation of T cells and associated
attacks on the central
nervous system. In
vitro, mice that received stem cells from older donors faced increased
central nervous system inflammation, demyelination
resulting in impaired
movement and cognition, and an increase in splenocytes compared to mice that
receive cells from younger donors.
"Aging is known to have a negative impact on the regenerative
capacity of most tissues, and human MSCs are
susceptible to biologic aging
including changes in differentiation potential, proliferation ability and gene
expression. These age-related differences
may affect the ability of older donor
cells to migrate extensively, provide trophic support, persist long-term and
promote repair mechanisms," said
Bunnell.
Bunnell notes that it's too early for these tests in mice to
provide much data about
the possible results in humans, though early data is
promising. The mice that received the MSC treatments were "pretty well
protected from disease
onset," he notes, adding that while some demonstrated
signs of disease, it was never as bad as in the mice who received mock
treatments or other stem
cells. While they haven't ascertained yet whether such
transplants could provide long-term benefit to patients, tests in mouse models
indicate that a
single dose can offer improvements for long periods of time, he
adds.
As they continue to pursue
this research, Bunnell says he'd
like to move this into human trials, as only small studies in human have been
done so far in the United States.
Additionally, he hopes to study the age
process more closely to figure out how age reduces the quality of the MSCs, and
if it is possible to alter
those processes.
Bunnell says that while these transplants probably don't
represent a cure—
noting that one is impossible "until we understand the
molecular pathology" of the disease—he does believe they will help to preserve
myelin and
"tremendously slow down the immune-mediated destruction associated
with the disease."
"While that may not be viewed as a
true cure for the
disease, I think we're going to allow people to have a much better life for
longer periods of time; they'd still have MS, but it's
not going to ravage them
the way it potentially would if we didn't give them stem cells," Bunnell
explains.
Code: E09251304 Back |
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