Adult stem cells activated in mammalian brain
Published: Thursday, July 24, 2008 - 12:29 in Biology & Nature
Adult stem cells originate in a different part of the brain than is
commonly believed, and with proper stimulation they can produce new
brain cells to replace those lost to disease or injury, a study by UC
Irvine scientists has shown. Evidence strongly shows that the true
stem cells in the mammalian brain are the ependymal cells that line
the ventricles in the brain and spinal cord, rather than cells in the
subventricular zone as biologists previously believed. Brain
ventricles are hollow chambers filled with fluid that supports brain
tissue, and a layer of ependymal cells lines these ventricles.
Knowing the cell source is crucial when developing stem cell-based
therapies. Additionally, knowing that these normally dormant cells
can be coaxed into dividing lays the groundwork for future therapies
in which a patient's own stem cells produce new brain cells to treat
neurological disorders and injuries such as Parkinson's disease,
stroke or traumatic brain injury.
"With such a therapy, we would know which cells in the body to target
for activation, and their offspring would have all the properties
necessary to replace damaged or missing cells," said Darius Gleason,
lead author of the study and a graduate student in the Department of
Developmental and Cell Biology. "It is a very promising approach to
stem cell therapy."
Study results appear this month online in the journal Neuroscience.
Stem cells are the "master cells" that produce each of the
specialized cells within the human body. If researchers could control
the production and differentiation of stem cells, they may be able to
use them to replace damaged tissues.
One focus of stem cell research is transplantation, which entails
injecting into the body healthy cells that may or may not genetically
match the patient. Transplantation of nonmatching stem cells requires
the use of drugs to prevent the body from rejecting the treatment.
But, working with a patient's own cells would eliminate the need for
transplantation and immunosuppressant drugs and may be a better
alternative, scientists say. Ependymal cells line the fluid-filled
ventricles, so a drug to activate the cells could theoretically
travel through this fluid directly to the stem cells.
"The cells already match your brain completely since they have the
same genetic make-up. That is a huge advantage over any other
approach that uses cells from a donor," Gleason said. "If they are
your cells, then all we are doing is helping your body fix itself.
We're not reinventing the repair process."
In this study, Gleason and Peter Bryant, developmental and cell
biology professor, used rats treated to develop the animal equivalent
of Parkinson's disease. They chose this type of rat because in a
previous study by UCI collaborator James Fallon, a small protein
given to the brain-damaged rats sparked a rapid and massive
production and migration of new cells, and significantly improved
motor behavior.
First, the UCI researchers sought to determine the true location of
stem cells in the rats by looking for polarized cells, which have
different sets of proteins on opposite sides so that when one divides
it can produce two different products. Polarization gives rise to
asymmetric cell division, which produces one copy of the parent and a
second cell that is programmed to turn into another cell type.
Asymmetric cell division is the defining characteristic of a stem
cell.
On rat brain samples, the researchers applied antibodies to identify
proteins that may be involved in asymmetric cell division, and they
found that polarization exists on the ependymal cells. "It couldn't
have been a stronger signal or clearer message. We could see that the
only cells undergoing asymmetric cell division were the ependymal
cells," Gleason said.
Next, they gave a drug to induce cell division in the rats and
examined their brains at intervals ranging from one to 28 days after
the treatment. At each interval, they counted cells that were
dividing in the ependymal layer. They found the most division at 28
days, when about one-quarter of the ependymal cells were dividing.
Previous studies by researchers at other institutions were successful
in getting only a few cells to divide in that layer.
"One interpretation of previous studies is there are scattered stem
cells in the ependymal layer, and it is hard to locate them," Bryant
said. "But we believe that all of the ependymal cells are stem cells,
and that they all have the ability to be activated."
Researchers don't know yet what sparks cell division at the molecular
level, but learning that process and how to control it could lead to
a safe, effective stem cell therapy.
Source: University of California - Irvine
http://esciencenews
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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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