ROBUST SURVIVAL OF ISOLATED BOVINE ADRENAL CHROMAFFIN CELLS FOLLOWINGINTRASTRIATAL TRANSPLANTATION - A NOVEL HYPOTHESIS OF ADRENAL GRAFT VIABILITY

Previous investigations have demonstrated that adrenal chromaffin cell s survive poorly when grafted into the striatum of rodents, nonhuman p rimates, and patients with Parkinson's disease. This poor survival has been attributed to the low levels of endogenous NGF within the striat um. However, chromaffin cells isolated from the nonchromaffin constitu ents of the adrenal medulla (fibroblasts and endothelial cells) have r ecently been demonstrated to survive grafting into a number of CNS sit es. The present study determined whether nonchromaffin constituents of the adrenal medulla may be responsible for poor graft survival. We co mpared the survival of intrastriatally grafted isolated bovine chromaf fin cells with that observed following implantation of either perfused adrenal medullary suspensions containing all adrenal medullary cell t ypes or isolated chromaffin cells that were then reseeded with autolog ous fibroblasts and endothelial cells. Implants of perfused adrenal me dullary cells survived poorly and most graft sites were infiltrated wi th macrophages. The chromaffin cells in this group that did survive ap peared to be in the process of degeneration. In contrast, large number s of isolated chromaffin cells survived for up to 2 months following t ransplantation. These cells maintained their endocrine phenotype and s tained for all enzymatic markers of catecholamine synthesis as well as chromogranin A. Morphologically, these cells resembled chromaffin cel ls seen in situ and the perigraft region was essentially devoid of mac rophages. When isolated chromaffin cells were reseeded with autologous fibroblasts and endothelial cells, the implants degenerated and few, if any, surviving chromaffin cells were observed. Interestingly, these latter grafts induced a host-derived sprouting response of tyrosine h ydroxylase-immunoreactive fibers. These data demonstrate that large nu mbers of adrenal chromaffin cells can survive intrastriatal implantati on in the absence of exposure to exogenous NGF. Rather, the nonchromaf fin cells of the adrenal medulla (fibroblasts and endothelial cells) a ppear to compromise the viability of grafted chromaffin cells. Once th ey are eliminated from the graft, robust survival of chromaffin cells occurs. If clinical trials employing adrenal medullary grafts are stil l to be considered for the treatment of Parkinson's disease, isolation of the chromaffin cells should be considered to enhance graft viabili ty.