O-2A glial progenitors from mature brain respond to CNS neuronal cell line-derived growth factors.
During development, myelin-forming oligodendrocytes and type 2 astrocytes are believed to arise from bipotential (O-2A) glial progenitors. Previously we found that conditioned medium (CM) from the B104 rat CNS neuronal cell line promotes growth of neonatal rat O-2A progenitors in serum-free culture conditions with subsequent increases in differentiated progeny. We now report that O-2A progenitors are present in mature rat brains and that this CM promotes the growth, motility, and bipolar morphology of these cells from 30- and 65-day-old rat brains, as shown by quantitative studies using double immunostaining and [3H]thymidine-autoradiography. In addition, the growth-promoting action of B104 CM is not neutralized by antibodies to platelet-derived growth factor, a proposed progenitor mitogen. Subsequent to the proliferation of these O-2A progenitors, increases in oligodendrocytes and type 2 astrocytes occur. These data suggest a novel therapeutic strategy for some demyelinating diseases, e.g., multiple sclerosis, where there is a deficit in oligodendrocytes. Although it has been proposed by others that mature brain O-2A progenitors are less proliferative and thereby incapable of adequately replenishing lost oligodendrocytes in these diseases, we present in vitro evidence for continued response of mature brain O-2A progenitors to this neuronal cell line-derived mitogen.
Hunter
S F
SF
Department of Pharmacology-Toxicology, University of Texas Medical Branch, Galveston 77550.
Bottenstein
J E
JE
D000818:Animals; D001345:Autoradiography; D001921:Brain / Q000166:cytology*; D002460:Cell Line; D002465:Cell Movement / Q000502:physiology; D002478:Cells, Cultured; D002490:Central Nervous System / Q000187:drug effects / Q000378:metabolism*; D003470:Culture Media; D005455:Fluorescent Antibody Technique; D008297:Male; D009414:Nerve Growth Factors / Q000494:pharmacology*; D009457:Neuroglia / Q000378:metabolism*; D009836:Oligodendroglia / Q000187:drug effects / Q000378:metabolism; D010641:Phenotype; D051381:Rats; D011919:Rats, Inbred Strains; D013234:Stem Cells / Q000378:metabolism*
D003470:Culture Media; D009414:Nerve Growth Factors