CelIuIar Transplantation for Intractable Pain

Abstract

Cellular transplantation may be a powerful approach for the alleviation of chronic pain. To study this, adrenal medullary chromaffin have been chosen as donor sources, because these cells produce and secrete catecholamines and opioid peptides, agents that reduce pain when administered directly into the spinal subarachnoid space and synergize to produce potent analgesia. In addition to these agents, chromaffin cells have been reported to secrete a variety of neurotrophic factors, cytokines, and other neuropeptides, as well as ascorbate and heme-containing proteins, which may aid in the restoration of spinal cord function in chronic pain syndromes. Donor sources for these studies have included primarily either adrenal medullary tissue allografts or isolated xenogeneic chromaffin cells, although cell lines that can be genetically engineered have been utilized. For preclinical rodent studies, allogeneic tissues can be obtained from adult donors of the same strain by microdissection of adrenal medullary tissue from the adrenal cortex. The latter approach has been utilized in initial clinical studies, with adrenal medullary tissue derived from human organ donors. However, the practical application of adrenal medullary implantation in clinical pain management is limited by the availability of allogeneic human donor tissue. Thus, xenogeneic chromaffin cells harvested from sources such as bovine adrenal glands may be an alternative. Another approach in xenotransplantation is the use of semipermeable polymer membranes to encapsulate xenogeneic cells and limit contact with the host immune system, while allowing diffusion of neuroactive substances and nutrients.