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---------------------------------------------------------------------------- Researchers unlocking mysteries of brain ---------------------------------------------------------------------------- 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> ---------------------------------------------------------------------------- [log in to unmask]