CYTOARCHITECTONIC DEVELOPMENT, AXON GLIA RELATIONSHIPS, AND LONG-DISTANCE AXON GROWTH OF PORCINE STRIATAL XENOGRAFTS IN RATS

Porcine fetal lateral ganglionic eminence cells were transplanted into the quinolinic-acid-lesioned corpus striatum of immunosuppressed adult rats. The resulting grafts were analyzed for graft development with respect to donor age, donor cell dosage, and survival time from 5 to 22 weeks postimplantation. Graft development is prolonged by a factor of 3-4 times in porcine xenografts as compared to rat allografts. As grafts matured, neuronal somata developed in clusters that expressed acetylcholinesterase (AChE), tyrosine hydroxylase, and dopamine- and cAMP-associated phosphoprotein. These clusters were interspersed with AChE-poor graft regions consisting of small densely packed cells that stained for glial fibrillary acidic protein and porcine cluster of differentiation factor 44 (a species-specific glial marker). Graft axons could be selectively stained for 70-kDa neurofilament and were preferentially associated with AChE-poor, glial-rich regions in younger grafts (8 weeks), but AChE-rich neuronal regions in older grafts (22 weeks). Both graft axons and graft glial fibers projected for long distances into the host internal capsule, external capsule, corpus callosum, and anterior commissure. Donor axons also innervated host target structures including the globus pallidus and substantia nigra. This demonstrates a prolonged development of striatal cells that is appropriate to the donor species and which produces long-distance target-specific axonal growth within the adult host brain. (C) 1994 Academic Press, Inc.