Brain Stem Cells Reverse Myelin Deficiency in Mice
By Jeffrey Perkel
HealthDay Reporter
Thursday, June 5, 2008; 12:00 AM
THURSDAY, June 5 (HealthDay News) -- Researchers report they have
used neural stem cells to correct a congenital brain disorder in
mice.
Dr. Steven Goldman, of the University of Rochester Medical Center in
New York, and his colleagues used a type of neural stem cell
called "glial progenitor cells" (GPCs), derived from human fetuses,
to correct both behavioral and physiological abnormalities in a mouse
model of a myelin-deficiency disorder.
The study represents "a very important advance," said Dr. James
Goldman, an investigator in the Columbia Neural Stem Cell Program at
Columbia University Medical Center, who was not involved in the
study.
Though Steven Goldman and others previously had shown that injection
of GPCs into mouse brains could lead to remyelination of demyelinated
neurons, that observation did not include any change in disease
progression.
"The fact that they were able to get at least some of these animals
to survive, and show that physiologically and behaviorally they are
doing well, is an advance," said James Goldman.
The findings were reported in the June issue ofCell Stem Cell.
Myelin is a structure, comprised of protein and fat, that envelops
long neuronal fibers called axons. Axons are the conduits for neural
impulses, both conscious and unconscious. Just as electrical cable
must be insulated to prevent signal loss over distance, myelin
ensures that nerve impulses can traverse long axonal processes in the
central nervous system without degrading.
Myelin is formed by neural support cells called oligodendrocytes,
which are derived from GPCs. Disorders that arise from the absence or
degradation of myelin represent a "substantial proportion of adult
neurological diseases," said Steven Goldman. They run the gamut, from
autoimmune disorders like muscular dystrophy, to lysosomal storage
diseases like Tay-Sachs, to congenital defects like Pelizaeus-
Merzbacher Disease, an X-linked condition where myelin doesn't form.
In this study, Goldman and his team used "shiverer" mice, whose
congenital lack of myelin basic protein causes them to shake and
seize uncontrollably, giving them their name. They typically die by 5
months of age.
The shiverer mice were crossed with immunodeficient mice, so they
would not reject the GPC transplant, and split into three treatment
groups; 59 received no treatment, 29 received injections of buffer
into five different locations in the brain shortly after birth, and
26 received injections of GPCs.
By about 130 days after birth, all 88 control mice died. But six of
26 transplanted animals survived at least 160 days, and four lived
over a year. Behaviorally and physiologically, these survivors
appeared largely cured, and post-mortem analysis of these animals'
brains and spinal cords demonstrated why.
"The entire central nervous system had remyelinated and looked normal
in terms of structural configuration of the myelination, both at the
microscopic and submicroscopic level, and at the behavioral level,"
Goldman said.
In other words, from five separate injection sites, the GPCs migrated
throughout the central nervous system, differentiated into
oligodendrocytes, and began producing myelin.
The researchers then assessed the physiological effect of that
remyelination, by measuring the speed of nerve transmission along
remyelinated axons. They observed velocities on par with those of
normal mice.
"That is proof in principle that putting glial progenitors in a brain
like this will at least partially remyelinate the brain, and do so
functionally,
Though this study involved a congenital pediatric disorder, Steven
Goldman said his goal is to apply the technique to adult diseases
like multiple sclerosis. For now, his team is working to understand
why most transplanted animals still die. He suggested this could stem
from the seizures that plague shiverer animals, including transplant
recipients that have not yet completed remyelination, and said he is
exploring the utility of pairing transplants with anticonvulsant
therapy to alleviate this problem.
But James Goldman pointed out that before this transplant procedure
can be turned into a clinical therapy, several issues must be
addressed, not the least of which is the politically sensitive
problem of obtaining and using human fetal tissue as a therapeutic
agent.
More information
For more on leukodystrophies, visit the U.S. National Library of
Medicine.
SOURCES: Steven Goldman, M.D., Ph.D., Dean Zutes Chair, professor,
Neurology and Neurosurgery, chief, Division of Cell and Gene Therapy,
and co-director, Center for Translational Neuromedicine, University
of Rochester Medical Center, Rochester, N.Y.; James E. Goldman, M.D.,
Ph.D., professor, pathology, and director, Division of
Neuropathology, Columbia University College of Physicians and
Surgeons, New York City; June 2008,Cell Stem Cell
http://www.washingt
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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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