Human oligodendrocyte precursor cells in vitro: phenotypic analysis and differential response to growth factors

Following experimental demyelination in rodents, oligodendrocyte precursor cells (OPCs) proliferate and differentiate into myelin-producing oligodendrocytes which effect robust remyelination. In contrast, remyelination in multiple sclerosis, the major human demyelinating disease, is generally limited and transient. Rodent OPCs have been well characterized in vitro and their response to growth factors documented. Since there appear to be appreciable species differences in OPC growth factor responsiveness, and since human precursors have proven difficult to culture, the present study has investigated mitogenic growth factors for cultured fetal human OPCs. Moreover, because markers for cultured human OPCs are not well established, we also examined which of the extensively used rodent OPC markers also label human precursors. Using a culture system modified for fetal human oligodendroglia, we have shown for the first time that the platelet-derived growth factor alpha receptor (PDGFalphaR) and A2B5 antigen are expressed together on human OPCs. Human precursors also expressed NG2 chondroitin sulfate proteoglycan, as did a proportion of O4+ preoligodendrocytes. Several growth factors known to affect rodent OPCs were tested and found to have similar effects on human cells. PDGF, neurotrophin 3 (NT3), and glial growth factor 2 (GGF2) promoted proliferation, while insulin-like growth factor-1 (IGF-1), exerted a maturational effect.