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

Abstract

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.

Neuronal Nitric Oxide Synthase Plays a Key Role in CNS Demyelination

“…Interestingly, although this impairment in remyelination was not correlated with a reduction in the number of OPCs in the lesioned areas, eNOS Ϫ/Ϫ mice upregulated IGF-1 mRNA levels to a lesser extent in response to cuprizone feeding. Several studies have pointed out to the important role that IGF-1 plays in the maturation of OPCs and therefore in the mechanisms leading to spontaneous remyelination after CNS trauma (Wilson et al, 2003).…”

The Influence of Platelet-Derived Growth Factor and Fibroblast Growth Factor 2 on Oligodendrocyte Development and Remyelination

“…However, several studies have also implicated PDGF as having a role in OLC differentiation as well as survival of OPs and newly generated oligodendrocytes (Barres et al, 1992;Allamargot et al, 2001;Wilson et al, 2003 FGF2 and FGF receptor (FGFR) levels are increased in demyelinated lesions and FGF2 signaling has significant effects during remyelination (Messersmith et al, 2000;Armstrong et al, 2002). In vivo, FGF2 acts as an inhibitor of OP differentiation during myelination as well as remyelination (Murtie et al, submitted).…”

“…With direct significance to the human context, OPs from human fetal tissue are responsive to PDGF and express PDGFαR (Zhang et al, 2000;Wilson et al, 2003).…”

Neural Stem Cells from Mammalian Brain: Isolation Protocols and Maintenance Conditions

“…The signaling pathway through the PDGF /PDGFR 14 has different effects depending on the stage of differentiation of these progenitors: it provides signals favoring proliferation and migration in murine and human oligodendrocyte progenitors (Wilson et al, 2003;Calver et al, 1998), whereas later in development is related with cell survival (Gogate et al, 1994). Similarly, FGF promotes proliferation and blocks differentiation of oligodendrocyte progenitors, in part through the modulation of PDGFR receptors expression (McKinnon et al, 1990).…”