Increased capacity for axonal outgrowth using xenogenic tissue in vitro and in a rodent model of Parkinson's disease

Background: It has previously been proposed that grafted neurons may have the potential for more extensive axonal outgrowth in a xenogenic environment, and may thus possess a primary advantage over allografts in central nervous system repair and circuit reconstruction. In order to directly address this issue, fibre outgrowth from primary dopaminergic neurons was examined both in vitro and in vivo in an allogenic or xenogenic environment. A combination of species was used to circumvent problems relating to different gestational/developmental periods for such cells. Methods: In the in vitro experiments, axon length was measured over 2 to 14 days in cultures derived from either rat or mouse ventral mesencephalon (VM) tissue co-cultured onto either a monolayer of the rat Neu7 inhibitory cell line or fetal rodent cortical tissue. In the in vivo experiments, fetal rat or mouse VM tissue was transplanted into the striatum or substantia nigra of 6-hydroxydopamine-lesioned athymic rats. Amphetamine-induced rotations were observed for 3 months post-transplantation and the degree of graft-mediated neurite outgrowth was analyzed. Results: Embryonic VM manifested a greater capacity for neurite formation and outgrowth on xenogenic tissue, which was shown to be significant using co-cultures of cortical cells. The transplantation study showed that xenograft-derived fibres had a greater capacity for extensive fibre projection compared with those originating from allografts. Conclusions: Results from the present study provide evidence for the hypothesis that xenografts are less responsive to inhibitory molecules present in the adult host environment and as such can project over great distances. Thus neural xenotransplantation may have the potential for more complete circuit reconstruction within the damaged host brain than equivalent allografted tissue.