Irvine, Calif., July
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
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
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
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
“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
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
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.
Fallon, psychiatry and human behavior professor, and researchers Magda Guerra
and Jian-Chang Liu contributed to this study. All of the scientists are
affiliated with the UCI Sue and Bill Gross Stem Cell Research Center.
Gleason’s work is supported by a stem cell training grant from the California
Institute for Regenerative Medicine. The UCI Office of Research, the Optical
Biology Core in the Developmental Biology Center, a gift from the Joseph’s
Foundation, and the UC MEXUS-CONACYT Postdoctoral Research Program also
supported this study.
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