Transplanted glial cells migrate over a greater distance and remyelinate demyelinated lesions more rapidly than endogenous remyelinating cells

Abstract

Glial cell transplantation offers a means of remyelinating areas of demyelination in situations where endogenous remyelination fails. How effective such a strategy would be if undertaken in human demyelinating disease is not yet clear since it is very difficult to create large areas of demyelination in adult rodents that would mimic the situation found in a human disease such as multiple sclerosis. When CNS tissue is subjected to 40 Grays of X-irradiation, remyelination is suppressed in the X-irradiated area unless cells migrate into, or are introduced into the X-irradiated area. In the present experiments, by appropriate positioning of lead shielding we have created a "starting gate" from which oligodendrocyte progenitors must depart in order to colonise areas of demyelination. When the starting gate is located at one end of the area of demyelination, endogenous cells fail to colonise throughout an area of demyelination over the ensuing month. In contrast, when transplanted oligodendrocyte precursors are faced with the same situation, the whole area of demyelination is remyelinated over the same period. To determine how far transplanted cells can migrate to areas of demyelination and also to study how quickly the cells can colonise areas of demyelination we injected cells at some distance from areas of demyelination made in X-irradiated tissue. In these experiments, we found that transplanted cells could repopulate up to 9 mm in 2 months compared to 4 mm recorded for endogenous cells (Franklin et al. [1997] J. Neurosci. Res. 50:337-344). These experiments demonstrate that transplanted cells have a far greater ability to colonise areas of demyelination than endogenous cells.