Oligodendrocyte-type 2 astrocyte (O-2A) progenitor cells from neonatal and adult rat optic nerve differ in their responsiveness to platelet-derived growth factor

Abstract

We have investigated, in vitro, the mitogenic responsiveness to platelet-derived growth factor (PDGF) of oligodendrocyte-type 2 astrocyte (O-2A) progenitor cells isolated from adult rat optic nerve and their differentiation into oligodendrocytes. Progenitor cells from adult optic nerves differentiate into oligodendrocytes in a limiting concentration of foetal calf serum more slowly than in cultures of neonatal cells. Nevertheless, differentiation of oligodendrocytes from progenitors is nearly complete by 6 days in vitro, with 50% expressing galactocerebroside by 4-5 days. In these experiments, adult optic nerve cells were grown in medium containing PDGF, a potent mitogen for neonatal O-2A progenitor cells, and yet the decline in numbers of O-2A progenitor cells matches the rise in oligodendrocyte numbers. We suggest that this is because adult O-2A progenitor cells differ from their neonatal counterparts and do not show the same proliferative response in the presence of exogenous PDGF. We tested this hypothesis by a quantitative autoradiographic analysis of tritiated thymidine-labelled nuclei, comparing percentages of labelled adult and neonatal O-2A lineage glial cells in low-serum medium, in the presence of absence of PDGF, with their response to a monolayer of neonatal rat cortical type 1 astrocytes or astrocyte-conditioned medium. Whereas, adult O-2A progenitors responded to astrocyte monolayers and to conditioned medium from astrocyte cultures, there was no dose-dependent response to PDGF-BB over a wide range of concentrations. Antibodies to human PDGF neutralise the growth-promoting activity of astrocyte-conditioned medium for neonatal O-2A cells but do not neutralise astrocyte-conditioned medium stimulation of adult O-2A progenitor cells. This indicates that the principal astrocyte-derived growth factor(s) for adult O-2A progenitor cells is unlikely to be PDGF.