ENHANCED SURVIVAL AND NEURONAL DIFFERENTIATION OF ADRENAL CHROMAFFIN CELLS COGRAFTED INTO THE STRIATUM WITH NGF-PRODUCING FIBROBLASTS

Although adrenal medullary chromaffin cells have been used extensively for intracerebral grafting, their survival has generally been poor. I mproved survival of the implanted cells has been achieved by exposing the chromaffin cells to NGF in vivo. Culture studies have shown, howev er, that chromaffin cells are converted into sympathetic neurons when NGF is included in the medium. The degree to which such a transdiffere ntiation may occur in vivo has not been determined. We assessed the ef fects of cografting chromaffin cells with primary fibroblasts genetica lly engineered to express NGF. Chromaffin cells from 10 d old rats wer e implanted with NGF-producing or beta-galactosidase-producing primary fibroblasts (control fibroblasts) into the striatum of 6-hydroxydopam ine treated adult rats of the same strain. Eight weeks postgrafting, c hromaffin cells cografted with NGF-producing fibroblasts displayed man y of the features of mature sympathetic neurons such a!; large somata, long processes, transmitter vesicles similar to those found in neuron s, and positive immunolabeling for the neuronal markers neurofilament, MAPS and SCG10. Chromaffin-derived neuron number was also significant ly enhanced in the presence of NGF-producing fibroblasts. While contro l fibroblasts were also found to increase chromaffin cell number above that of chromaffin cells grafted alone, the control fibroblasts did n ot induce neuronal transdifferentiation. These results demonstrate tha t chromaffin cells cografted with NGF-producing fibroblasts undergo tr ansdifferentiation in vivo and express many characteristics of mature sympathetic neurons. The consequences of this transdifferentiation on the long term survival and function of the transplanted cells in vivo remain to be clarified.