Progress Towards Inducing Greater Remyelination
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Nerves are sheathed in myelin. That sheathing deteriorates to some degree with age, and more dramatically in demyelinating conditions such as multiple sclerosis (MS). Some of the approaches taken by researchers working on conditions such as MS may prove applicable to reversal of the lesser deterioration of myelin in aging, a process that correlates with some forms of cognitive decline.

Stem cell therapy is seen as having dramatic potential for treating MS, but there are key obstacles, especially the length of time it takes for progenitor cells to turn into oligodendrocytes, the brain's myelin-making cells. Using currently available methods, it can take as long as a year to generate a sufficient number of human oligodendrocyte cells to treat a single MS patient. That's partly because there are so many steps: the skin or blood cell must be turned into induced pluripotent stem cells, which can differentiate into any other type of cell and from which neural progenitor cells can be produced. Those progenitor cells then must undergo differentiation to oligodendrocyte progenitors that are capable of ultimately producing the oligodendrocytes.

Using fetal brain stem cells, the researchers searched for transcription factors that are absent in neural progenitor cells and switched on in oligodendrocyte progenitor cells. While neural progenitor cells are capable of producing myelin, they do so very poorly and can cause undesirable outcomes in patients, so the only candidate for transplantation is the oligodendrocyte progenitor. "The question was, could we use one of these transcription factors to turn the neural progenitor cell into an oligodendrocyte progenitor cell?"

"We narrowed it down to a short list of 10 transcription factors that were made exclusively by oligodendrocyte progenitor cells. Among all 10 factors that we studied, only SOX10 was able to make the switch from neural progenitor to oligodendrocyte progenitor cell." In addition, the researchers found that SOX10 could expedite the transformation from oligodendrocyte progenitor cell to differentiation as an oligodendrocyte, the myelin-producing cell and the ultimate treatment goal for MS. "Ideally, we'd like to get directly to oligodendrocyte progenitors. The new results are a stepping stone to the overall goal of being able to take a patient's skin cells or blood cells and create from them oligodendrocyte progenitors."


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