PURIFICATION AND CHARACTERIZATION OF ADULT OLIGODENDROCYTE PRECURSOR CELLS FROM THE RAT OPTIC-NERVE

Oligodendrocyte precursor cells (OPCs) persist in substantial numbers in the adult brain in a quiescent state suggesting that they may provi de a source of new oligodendrocytes after injury. To determine whether adult OPCs have the capacity to divide rapidly, we have developed a m ethod to highly purify OPCs from adult optic nerve and have directly c ompared their properties with their perinatal counterparts. When cultu red in platelet-derived growth factor (PDGF), an astrocyte-derived mit ogen, perinatal OPCs divided approximately once per day, whereas adult OPCs divided only once every 3 or 4 d. The proliferation rate of adul t OPCs was not increased by addition of fibroblast growth factor (FGF) or of the neuregulin glial growth factor 2 (GGF2), two mitogens that are normally produced by retinal ganglion cells. cAMP elevation has be en shown previously to be essential for Schwann cells to survive and d ivide in response to GGF2 and other mitogens. Similarly we found that when cAMP levels were elevated, GGF2 alone was sufficient to induce pe rinatal OPCs to divide slowly, approximately once every 4 d, but adult OPCs still did not divide. When PDGF was combined with GGF2 and cAMP elevation, however, the adult OPCs began to divide rapidly. These find ings indicate that adult OPCs are intrinsically different than perinat al OPCs. They are not senescent cells, however, because they retain th e capacity to divide rapidly. Thus, after demyelinating injuries, enha nced axonal release of GGF2 or a related neuregulin might collaborate with astrocyte-derived PDGF to induce rapid division of adult OPCs.