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Researchers unlocking mysteries of brain
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Copyright 1997 Nando.net            Copyright 1997 Scripps-McClatchy Western

SALT LAKE CITY (August 1, 1997 10:21 a.m. EDT) -- Scientists dream of
repairing spinal-cord injuries so the disabled can walk again, and of
fixing the brain to reverse the ravages of Alzheimer's, Parkinson's and
other neurodegenerative diseases.

Before it is possible to mend a damaged central nervous system, researchers
first must learn how the brain and spinal cord are assembled in developing
embryos.

A small but unprecedented step toward that goal has been taken by two
University of Utah researchers. Developmental biologist Margot
Mayer-Proschel and physician-neuroscientist Mahendra Rao will publish their
findings Friday in the journal "Developmental Biology."

Their study deals with "multipotential neuroepithelial stem cells." Such
cells are found in embryos and can divide to produce all major cell types
found in the nervous system, including:

-- Neurons, nerve cells that transmit signals.

-- Astroyctes, cells that form the support structure in the brain and
spinal cord.

-- Oligodendrocytes, cells that produce myelin, the insulation that coats
neurons.

Stem cells are precursor or "multipotential" cells because there are
multiple potential possibilities of what kind of adult cell they will
become, including neurons, astrocytes and oligodendrocytes.

Mayer-Proschel and Rao showed that when grown in culture, stem cells also
can produce intermediate cell types -- something long believed but never
proved until now.

"These are cells which can still make more than one cell type and can still
divide, but cannot make all cell types anymore," said Mayer-Proschel.

The Utah researchers took stem cells from the developing spinal cords of
rat embryos. They demonstrated those cells could become an intermediate
cell called a glioblast, which is capable of becoming an astrocyte or
oligodendrocyte, but can't become a neuron. They soon will publish another
study showing stem cells also can generate intermediate cells capable of
producing only neurons.

"We are showing how different kinds of cells that make a brain find their
identities," said Mayer-Proschel. "A brain has a lot of different cells.
Brain structure develops quite late in the embryo. We want to understand
how, when and where does a (precursor) cell decide what cell to become in
the brain."

The Utah study "is the first demonstration you can generate the
intermediate cell from a multipotential cell and maintain it in culture,"
said Ronald McKay, molecular-biology lab chief at the National Institute of
Neurological Disorders and Stroke. "That's a nice finding. ... There's a
lot of work going on now trying to understand how cell types are derived
from one another in the central nervous system."

Neurons and other mature nervous-system cells don't divide and copy
themselves. So huge numbers of such cells would have to be transplanted to
repair an injured or diseased brain or spinal cord.

Stem cells, however, copy themselves indefinitely. That is how they
generate enough neurons, astroyctes and oligodendrocytes to form the brain
and spinal cord in a developing embryo. If nervous-system stem cells could
be transplanted, a small number could divide and grow into enough mature
cells to repair the damage, Mayer-Proschel said.

She said such transplants might be used for degenerative nervous-system
diseases -- including Alzheimer's, multiple sclerosis, Huntington's and
Parkinson's -- and for spinal-cord and brain injuries.

Learning how embryonic stem cells develop into mature cells in the brain
and spinal cord also may improve understanding and treatment of tumors,
said Mayer-Proschel, an assistant professor at the U.'s Huntsman Cancer
Institute.

Mature nervous-system cells like neurons don't divide. Cancer is run-amok
cell growth. So brain cancers likely originate in cells that are dividing,
such as intermediate cells, she added. Identifying such cells ultimately
may help doctors better aim chemotherapy at cells where cancer begins.

"If we know how a brain is assembled the right way, we have a good chance
to know what went wrong when you get a tumor, which is assembling the wrong
way," Mayer-Proschel said.

She predicted it will take five years to learn if it is feasible to
transplant stem cells or intermediate cells to repair brain and spinal-cord
damage. Her study showed it is possible to purify intermediate cells and
maintain them in culture -- something necessary if they are used for
transplants.

California Institute of Technology neurobiologist Marianne Bronner-Fraser,
an editor of Developmental Biology, said the Utah study is "interesting,
and there are certainly some potential clinical applications for
repopulating damaged regions of the brain" with transplanted cells.

"I don't believe it's pipe-dreamish at all," McKay said. "But it's likely
to take several years to become an effective treatment for any
central-nervous-system disease."

A crude transplant was performed July 11 when University of Florida
researchers injected a paralyzed man with pieces of spinal cord from
aborted to 9-week-old embryos. The surgeons said they only hoped to plug a
cavity in the man's spinal cord to prevent further damage, not restore his
lost feeling and mobility.

"It's one thing to get the nerve to grow where the injury took place, and
it's another thing to remyelinate that nerve with coating so you can
transmit a signal," Mayer-Proschel said.

She foresees the possibility of more precise repairs in which
nervous-system intermediate cells would be transplanted for a specific
task. For example, intermediate cells might be transplanted so they
generate oligodendrocytes, which would produce myelin to recoat damaged
nerves. That might be a treatment for multiple sclerosis, a disease marked
by the loss of myelin coating on the brain and spinal cord.

Discovery of stem cells in the central nervous system is fairly recent,
with good evidence of their existence only since 1990, McKay said.

Better-known stem cells are found in bone marrow. They serve as factories
for red and white blood cells and platelets. Bone marrow and commercially
prepared stem cells are transplanted into people to replace blood cells
destroyed by blood diseases or leukemias and other cancers. Such
transplants also restore stem cells destroyed by chemotherapy or radiation.

Mayer-Proschel said other stem cells produce smooth muscle, liver, pancreas
and other tissues.

During a recent biology conference at Snowbird, a Johns Hopkins University
researcher reported he had isolated the ultimate human embryonic stem cells
from aborted fetuses. These "mothers of all stem cells" can develop into
nerves, blood, muscle or any other organ, and also might be used to replace
damaged or diseased tissues.

By LEE SIEGEL, Salt Lake Tribune
<http://www.nando.net/newsroom/ntn/health/080197/health5_29421.html>
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