Researchers Reprogram Adult Stem Cells in Mouse Brain to Become Myelin-Making Cells

--After much further research, a similar approach may someday be used to repair myelin lost in MSResearchers report that adult stem cells in mice that are on their way to becoming nerve cells can be redirected by changing a single gene to turn into cells that make nerve fiber-insulating myelin – the substance that is a key target of the immune attack in MS. Fred Gage, PhD (The Salk Institute for Biological Studies, LaJolla) Sebastian Jessberger, PhD (now at Swiss Federal Institute of Technology) and colleagues report their findings in Nature Neuroscience (June 29, 2008, electronic publication ahead of print). Further research is needed to translate these findings in people and to determine their significance to myelin repair in MS. The study was funded by multiple agencies including the National Institutes of Health.

Background: The possibility of repairing myelin that is damaged in MS is being explored onmany fronts. The cells that make myelin are often destroyed, limiting their capacity to repair the damage. One therapeutic strategy under study is to stimulate spare, immature cells that reside in the adult brain to move to areas of damage and repair myelin.

One source being explored is neural (nerve) stem cells, including those that reside in a part of the brain called the hippocampus. When neural stem cells are grown in the laboratory and provided with various growth factors, scientists have been able to switch their growth into several types of brain cells including myelin-making cells. Taking the next step, Dr. Gage’s team sought to determine if it would be possible to direct the fate of neural stem cells in their natural environment: the brain.

The Study/Results: In one group of mice, the team injected a virus that had been programmed to carry the human gene called “Ascl1” into the hippocampus to force increased activity of this gene. Ascl1 has been associated with myelin-making cell development. Indeed, in these mice – unlike the control mice without the overly active Ascl1 – neural stem cells were induced to develop into myelin-making cells. The team did a series of tests to show they had indeed changed the fate of the neural stem cells.

This study confirms that adult stem cells in the brain retain their ability to be converted to certain other types of brain cells. “The finding that a single gene can control whether these cells will go down the nerve or myelin-making pathway is very exciting,” said John R. Richert, MD, executive vice president of Research & Clinical Programs for the National MS Society. “These findings in mice represent a leap forward in developing ways to redirect repair cells in the brain. Further research is needed to translate these findings into human studies and to determine their significance to the goal of repairing the damaged nervous system in people with MS.”