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 subsequen t to transplantation in the peripheral and central nervous system of a dult rats. In the brain, MAK cell survival depended on the secretion o f ciliary neurotrophic factor (CNTF) by co-grafts of genetically modif ied glioma cells. No trophic factor supplement was required for develo pment of the MAH cells in the peripheral nerve environment. Transplant ed progenitor cells withdrew from the cell cycle within 48 h and diffe rentiated into a prominent population of large sympathetic-like neuron s, The neurons expressed the a subunit of the CNTF receptor and approp riate spatial distributions of cytoskeletal proteins and catecholamine related enzymes. The results identify a role for CNTF in the developm ent of the sympathoadrenal cell lineage and support the concept of imm ortalized progenitor cells as alternatives to primary cells for cell r eplacement strategies in the nervous system.