Long-term culture of purified postnatal oligodendrocyte precursor cells: Evidence for an intrinsic maturation program that plays out over months

Oligodendrocytes myelinate axons in the vertebrate central nervous system ( CNS). They develop from precursor cells (OPCs), some of which persist in th e adult CNS. Adult OPCs differ in many of their properties from OPCs in the developing CNS. In this study we have purified OPCs from postnatal rat opt ic nerve and cultured them in serum-free medium containing platelet-derived growth factor (PDGF), the main mitogen for OPCs, but in the absence of thy roid hormone in order to inhibit their differentiation into oligodendrocyte s. We find that many of the cells continue to proliferate for more than a y ear and progressively acquire a number of the characteristics of OPCs isola ted from adult optic nerve. These findings suggest that OPCs have an intrin sic maturation program that progressively changes the cell's phenotype over many months. When we culture the postnatal OPCs in the same conditions but with the addition of basic fibroblast growth factor (bFGF), the cells acqu ire these mature characteristics much more slowly, suggesting that the comb ination of bFGF and PDGF, previously shown to inhibit OPC differentiation, also inhibits OPC maturation. The challenge now is to determine the molecul ar basis of such a protracted maturation program and how the program is res trained by bFGF.