Stem cells in the brain may be able to produce new brain cells to replace those lost to disease or injury, UC Irvine scientists have found. They've also found that these 'true' stem cells are located in a different part of the brain than believed previously.
They say 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.
Brain ventricles are hollow chambers filled with fluid that supports brain tissue, and a layer of ependymal cells lines these ventricles.
The knowledge 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. It is a very promising approach to stem cell therapy," said Darius Gleason, lead author of the study and a graduate student in the Department of Developmental and Cell Biology.
Stem cells are the "master cells" that produce each of the specialized cells within the human body and they may be used to replace damaged tissues. However, 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. If they are your cells, then all we are doing is helping your body fix itself. We're not reinventing the repair process," said Gleason.
In the study, the researchers used rats treated to develop the animal equivalent of Parkinson's disease. They first 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.
The researchers applied antibodies on rat brain samples 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," said Gleason.
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. But we believe that all of the ependymal cells are stem cells, and that they all have the ability to be activated," said Bryant.
The results of the study appear this month online in the journal Neuroscience.