Peripheral nerve segments promote consistent long-term survival of adrenal medulla transplants in the brain

Patients with Parkinson's disease have received intracerebral transplants of autologous adrenal medulla in the attempt to counteract their severe motor dysfunctions. Unfortunately, in the majority of cases, clinical improvement has not persisted and there has been extremely poor survival of the grafts. Based on the recent observations of long-term viability of adrenal medulla grafts in the interior of transected peripheral nerves, adrenal medulla/peripheral nerve complexes were constructed in the brain to promote extended viability of chromaffin cells. A three-step, time-dependent transplantation procedure is described that results in a 100% survival rate of the adrenal medulla graft. The grafts consist of a stable population of approximately 2.0 x 10(3) chromaffin cells that survive for at least 6 months (longest time point studied): Immunoreactivity to catecholamine-related enzymes (tyrosine hydroxylase, dopamine beta-hydroxylase) and the low-affinity NGF receptor (192-IgG) are expressed by the chromaffin cells. The ultrastructural characteristics of the cells are normal and comparable to their in vivo counterparts. Construction of these peripheral nerve/adrenal medulla complexes evidently improves local conditions in and around the grafts, enabling the chromaffin cells to remain viable. This new methodology achieves the goal of reliable and extended survival of the adrenal medulla graft after intracerebral transplantation. The enhanced longevity now provides an opportunity to reevaluate the efficacy of the adrenal medulla transplant to ameliorate the functional disorders associated with striatal dopamine depletion, especially over long time periods.