Neural Transplantation and Trophic Factors in Parkinson's Disease: Special Reference to Chromaffin Cell Grafting, NGF Support from Pretransected Peripheral Nerve, and Encapsulated Dopamine-Secreting Cell Grafting

Abstract

Since adrenal medullary chromaffin cells produce catecholamines as well as several kinds of neurotrophic factors which affect dopamine neurons, the authors have investigated the methods to increase the survival of grafted chromaffin cells in parkinsonian model animals. Measurement of nerve growth factor (NGF) showed that NGF level at the distal stump of the pretransected peripheral nerve increased significantly, thus, we have applied cografting of chromaffin cells with this stump of the peripheral nerve to animal models of Parkinson's disease since chromaffin cell survival have been reported to be increased by supplementation of nerve growth factor (NGF)in vitroandin vivo.By this cografting approach, not only the chromaffin cell survival but also the host intrinsic dopaminergic system recovery were enhanced. This effect continued 2 years in our long-term study. The effects of donor and host ages were investigated and the results showed that the effects were more prominent when young donors or hosts were used compared with aging donors or hosts. Although cografting of adrenal medulla with peripheral nerve was applied successfully in parkinsonian patients with favorable results, it may be difficult to apply this procedure in aged patients since this is autografting and adrenal medulla itself may be affected by the disease in aged patients. Polymer-encapsulated dopamine-secreting cells are another donor candidates and can be applied combined with stereotaxic thalamotomy or pallidotomy for the patients with Parkinson's disease in the near future.