Transplantation of Embryonic Porcine Neocortical Tissue into Newborn Rats

Abstract

Several previous studies, suggesting the potential use of embryonic xenografts in the treatment of neurological disorders, indicate that neural growth and axonal guidance factors may function across species. In this light, blocks of fetal porcine neocortex were grafted into small cortical lesion cavities made in newborn rats. Sacrifice at 3–12.5 weeks posttransplantation revealed healthy looking grafts in several animals. Apparent graft rejection evidenced by areas of necrosis and OX1 reactivity was observed in some of the older transplants. Treatment of nursing mothers or of postweaning newborns with cyclosporin A did not appear to promote graft survival. Some transplants grew to extremely large proportions and were characterized by bands of cells and bundles of axons as observed using immunohistochemical staining for pig neurofilament. Neurofilament-positive axons projected from several of the grafts to course through the corpus callosum to the contralateral cortex or to course ipsilaterally within the subcortical white matter, where labeled fibers could be traced to the midbrain crus cerebri in older transplants. Bundles of axons were also observed coursing within the ipsilateral caudate putamen where terminal branching was apparent. The normal course of transplant efferents within the host brain indicates that growing pig axons can respond to rodent axonal guidance factors.