Biological and Molecular Approaches to the Generation of Conditionally Immortal Neural Cells

The ability to generate expanded populations of individual cell types able to undergo normal differentiation in vitro and in vivo is of critical importance in the investigation of the mechanisms that underlie differentiation and in studies on the use of cell transplantation to repair damaged tissues. This review discusses two different approaches to the generation of expanded cell populations with phenotypes useful for either of these purposes. In one line of research, an analysis of the growth control properties of glial precursor cells of the CNS has revealed that cooperation between appropriate mitogens can promote extended precursor division in the absence of differentiation, thus allowing unprecedented expansion of a primary cell population without resort to the expression of activated oncogenes in the cells of interest. In a second line of research, H-2K^btsA58 transgenic mice have been developed in order to allow the direct derivation of conditionally immortal cell lines from many tissues of the body simply by dissection and growth of cells under permissive conditions. In both instances, cells grown for extended periods in vitro displayed normal patterns of differentiation when reintroduced in vivo. In addition, conditionally immortal astrocytes derived from H-2K^btsA58 mice appear to offer a simple cellular model for studying the ability of glial scar tissue to inhibit migration of glial precursor cells and extension of neurites from mature neurons.