TROPHIC EFFECTS OF BASIC FIBROBLAST GROWTH-FACTOR (BFGF) ON DIFFERENTIATED OLIGODENDROGLIA - A MECHANISM FOR REGENERATION OF THE OLIGODENDROGLIAL LINEAGE

We have investigated the effect of basic fibroblast growth factor (bFG F) on the proliferation and phenotype of differentiated oligodendrogli a. Using primary cell cultures enriched in oligodendrocytes but contai ning few O2A-oligodendrocyte progenitor cells, we demonstrate that bFG F treatment greatly increases the proportion of O2A cells while decrea sing the proportion of galactocerebroside + (GalC+), myelin basic prot ein +(MBP+) oligodendrocytes, and the steady state levels of MPB mRNA. Complement mediated cell lysis experiments using the A2B5 antibody to deplete existing O2A cells or the R-Mab antibody to deplete existing oligodendroglia show that bFGF elicits a rapid increase in the number of O2A cells in cultures previously depleted of O2A cells, but does no t cause an early increase in O2A cells in cultures from which oligoden droglia had been removed, indicating that the oligodendrocytes are the source of the newly recruited O2A cells. This bFGF-mediated transitio n from oligodendrocyte to O2A cells occurs with a time course similar to the bFGF-induced increase of the proliferation rate of the GalC+ ol igodendrocytes. Studies with purified, passaged cells of the oligodend roglial lineage show that bFGF augments oligodendroglial dedifferentia tion and proliferation in chronologically adult oligodendrocytes and i n the virtual absence of other cell types. We have thus demonstrated t hat mature oligodendrocytes are induced by bFGF to dedifferentiate and proliferate, suggesting a mechanism for regeneration of the oligodend roglial lineage following demyelinating disease. (C) 1993 Wiley-Liss, Inc.