Ciliary neurotrophic factor promotes the terminal differentiation of v-myc immortalized sympathoadrenal progenitor cells in vivo

Survival and differentiation of a sympathoadrenal progenitor cell line (termed MAH), transduced with a v-myc oncogene, was studied subsequent to transplantation in the peripheral and central nervous system of adult rats. In the brain, MAH cell survival depended on the secretion of ciliary neurotrophic factor (CNTF) by co-grafts of genetically modified glioma cells. No trophic factor supplement was required for development of the MAH cells in the peripheral nerve environment. Transplanted progenitor cells withdrew from the cell cycle within 48 h and differentiated into a prominent population of large sympathetic-like neurons. The neurons expressed the alpha subunit of the CNTF receptor and appropriate spatial distributions of cytoskeletal proteins and catecholamine related enzymes. The results identify a role for CNTF in the development of the sympathoadrenal cell lineage and support the concept of immortalized progenitor cells as alternatives to primary cells for cell replacement strategies in the nervous system.