Transplantation of fetal spinal cord tissue into the chronically injured adult rat spinal cord.

Transplants of fetal central nervous system (CNS) tissue into the acutely injured rat spinal cord have been demonstrated to differentiate and partially integrate with the adjacent host neuropil. In the present study, we examined the potential for applying a transplantation approach to chronic spinal cord lesions. In particular, we were interested in learning whether host-graft fusion would be adversely affected by an advanced histopathology characterized in part by glial scar formation. Hemisection cavities were prepared at lumbar levels of the adult rat spinal cord 2-7 weeks prior to the transplantation of spinal cord tissue obtained from 14-day rat fetuses. Graft survival, differentiation, and integration with the host spinal cord were subsequently evaluated by light microscopic techniques at post-transplantation intervals of 1-6 months. Immunocytochemistry was also employed to examine the extent of astrocytic scar formation at the host-graft interface and serotoninergic innervation of the grafts. In some other cases, anterograde and retrograde transport of wheat germ agglutinin-conjugated horseradish peroxidase was used to determine whether axonal projections were formed between the host spinal cords and grafts. By 2 weeks after injury the initial lesion cavities were surrounded by a continuous astrocytic scar which remained intact for at least 7 weeks after injury in nongrafted control animals. In other animals, transplantation into these advanced lesions resulted in well-differentiated grafts with a 90% long-term survival rate. Although dense gliosis was still present along the lesion surfaces of the recipient spinal cord, foci of confluent host-graft neuropil were observed where interruptions in the scar had occurred. Donor tissue integrated most often with the host spinal cord at interfaces with host gray matter; however, some implants also exhibited sites of fusion with damaged host white matter. Thus, some regions of confluent graft and host neuropil could be routinely identified, despite the presence of a dense glial scar along the walls of the chronic lesion site at the time of transplantation. Anterograde and retrograde tract-tracing results suggested that some axonal projections into these grafts had originated from host neurons located immediately adjacent to the donor-recipient interface. In addition, immunocytochemistry revealed some host serotoninergic axons (presumably of supraspinal origin) traversing nongliotic interfaces. The results of this study raise the possibility that grafted fetal CNS tissue has a capacity for stimulating partial regression of an established glial scar.(ABSTRACT TRUNCATED AT 400 WORDS)