Findings May Lead to Improved Treatments for Parkinsonís Disease, Other Disorders
Recent advances in understanding adult CNS stem cells are reviewed in the April 4, 1997, issue of Science1 by Ronald D.G. McKay, Ph.D., chief of the Laboratory of Molecular Biology at the National Institute of Neurological Disorders and Stroke (NINDS) in Bethesda, Maryland. In another recent paper 2, Dr. McKay and his colleagues provided the first detailed evidence that adult and fetal stem cells behave in a uniform way. These findings suggest that what scientists are learning about the complex molecular steps controlling fetal development may be directly applied to repair of the damaged adult nervous system.
"We need to understand the chemical signals, or language, that cells use to control differentiation into different types of cells," says Dr. McKay. "While previous evidence suggested that there were stem cells in the adult, there was no information about how to control them." Learning that adult stem cells are essentially the same as fetal stem cells is the latest in a string of findings revealing that the adult CNS is actually quite malleable, or "plastic."
Stem cells are the beginning of the story of development, "like the Garden of Eden," says Dr. McKay. A single CNS stem cell can differentiate, or change during cell division, into any of the three major cell types in the brain and spinal cord: neurons, astrocytes, and oligodendrocytes. This differentiation occurs naturally during fetal development, ultimately giving rise to the marvelously complex human nervous system. For unknown reasons, however, most CNS stem cells in adults do not normally differentiate.
Dr. McKay and others recently discovered that purified CNS stem cells will divide in culture if given one of several growth factors. This will allow scientists to move from a "hunter-gatherer" stage, where they search out a limited supply of stem cells, to a "settled agriculture" stage, where they can use systematic technology to grow their own supply, Dr. McKay says.
The newly developed ability to culture large numbers of purified stem cells allows scientists to study the specific roles chemical signals play in brain development. For example, Dr. McKay and his colleagues have found that one protein instructs cultured stem cells to differentiate into neurons, while others lead to astrocyte and oligodendrocyte development. This knowledge should ultimately allow researchers to manipulate adult CNS stem cells and use them to replace cells that have been lost to injury or disease.
One of the most immediate applications for the new knowledge about stem cells may be to improve treatment for Parkinsonís disease. Early fetal transplant studies have shown that transplanted cells can survive in the brains of Parkinsonís patients and partially restore function. Using the new information from Dr. McKay and others, researchers may now be able to culture stem cells to repair damaged parts of the brain and spinal cord. These stem cells might also be genetically altered to produce substances important to normal CNS function. Eventually, scientists may even be able to eliminate the need for transplants by pharmacologically manipulating the stem cells normally present in the CNS.
This research may also lead to new ways of stopping the growth of brain tumors. Putting genes that control cancer susceptibility into a stem cell culture would allow scientists to learn how these genes function in a controlled situation.
The next step, says Dr. McKay, is to learn why CNS stem cells in adults do not differentiate as easily in the body as they do in culture. Scientists also need to learn what adult stem cells normally do in the CNS. Answering these questions may not only point to ways of repairing the damaged nervous system, but may also help researchers understand normal aging.
The NINDS, one of the National Institutes of Health located in Bethesda, Maryland, is the nationís leading supporter of research on the brain and nervous system and a lead agency for the Congressionally designated Decade of the Brain.
(This release will be available on the World Wide Web at http://www.ninds.nih.gov).
2Johe, K.; Hazel, T.G.; Muller, T.; Dugich-Djordjevic, M.M.; McKay, R.D.G. "Single Factors Direct the Differentiation of Stem Cells From the Fetal and Adult Central Nervous System." Genes and Development, Vol. 10, 1996 (pp. 3129-3140).