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 (bFGF) on the proliferation and phenotype of differentiated oligodendroglia. Using primary cell cultures enriched in oligodendrocytes but containing few O2A-oligodendrocyte progenitor cells, we demonstrate that bFGF treatment greatly increases the proportion of O2A cells while decreasing the proportion of galactocerebroside +(GalC+), myelin basic protein +(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 not cause an early increase in O2A cells in cultures from which oligodendroglia had been removed, indicating that the oligodendrocytes are the source of the newly recruited O2A cells. This bFGF-mediated transition from oligodendrocyte to O2A cells occurs with a time course similar to the bFGF-induced increase of the proliferation rate of the GalC+ oligodendrocytes. Studies with purified, passaged cells of the oligodendroglial lineage show that bFGF augments oligodendroglial dedifferentiation and proliferation in chronologically adult oligodendrocytes and in the virtual absence of other cell types. We have thus demonstrated that mature oligodendrocytes are induced by bFGF to dedifferentiate and proliferate, suggesting a mechanism for regeneration of the oligodendroglial lineage following demyelinating disease.
Grinspan
J B
JB
Division of Neurology Research, Children's Hospital of Philadelphia, PA 19104.
Stern
J L
JL
Franceschini
B
B
Pleasure
D
D
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D015152:Blotting, Northern; D001921:Brain / Q000166:cytology; D001973:Bromodeoxyuridine; D002454:Cell Differentiation; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D003165:Complement System Proteins / Q000502:physiology; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology*; D007150:Immunohistochemistry; D004676:Myelin Basic Protein / Q000096:biosynthesis; D009416:Nerve Regeneration / Q000187:drug effects*; D009836:Oligodendroglia / Q000187:drug effects* / Q000502:physiology; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology; D051381:Rats
D000911:Antibodies, Monoclonal; D004676:Myelin Basic Protein; D010982:Platelet-Derived Growth Factor; D016222:Fibroblast Growth Factor 2; D003165:Complement System Proteins; D001973:Bromodeoxyuridine