LINES OF GLIAL PRECURSOR CELLS IMMORTALIZED WITH A TEMPERATURE-SENSITIVE ONCOGENE GIVE RISE TO ASTROCYTES AND OLIGODENDROCYTES FOLLOWING TRANSPLANTATION INTO DEMYELINATED LESIONS IN THE CENTRAL-NERVOUS-SYSTEM

Immortalised lines of murine glial precursor cells expressing the neomycin resistance gene and a temperature-sensitive mutation of the SV 40 T oncogene were established from cultures of oligodendrocytes and precursor cells infected with a replication-incompetent, helper-free retrovirus. At the permissive temperature (33-degrees-C), they could be continually propagated in vitro and cells were present expressing the 04 antigen specific for glial precursor cells and oligodendrocytes. At 38-degrees-C, where the expression of the T antigen is down regulated, cell division largely ceased. During early passage in vitro, limited differentiation to a more mature phenotype, as evidenced by expression of GFAP and the oligodendrocyte marker 01 was observed at both 33-degrees-C and 38-degrees-C. When transplanted into demyelinating lesions in the spinal cords of adult rats early passages of the lines yielded myelin-forming oligodendrocytes and astrocytes. Cells from later passages of the lines although failing to synthesise myelin still associated specifically with the demyelinated axons. These experiments demonstrate the retention of physiological properties of these oncogene-carrying glial cells when transplanted in vivo and suggest that such immortalised populations can be used for the isolation of molecules regulating glial cell function. (C) 1993 Wiley-Liss, Inc.