Development of embryonic spinal cord transplants in the rat

Abstract

Although fetal brain tissue, grafted into the CNS of neonatal and adult animals, has been shown to survive and differentiate, relatively little information has been obtained regarding the development of embryonic spinal cord transplants, especially in the injured host CNS. The survival and differentiation of fetal spinal cord transplants in either intracerebral cavities or the lateral ventricles of the adult rat brain were thus examined with light and electron microscopy. Approximately 90% of the spinal cord implants taken from 12–15-day fetuses persisted in either transplantation site with some surviving for as long as 8 months (latest interval studied). The survival rate was considerably lower (22%), however, with tissues obtained from older fetuses. Within 3 weeks, the transplants obtained from 12–15-day donors had become extensively myelinated and contained many neurons of different sizes, including some clusters of large neurons resembling ventral horn cells of the intact spinal cord. In addition, all of the mature grafts were characterized by multiple myelin-free regions of neuropil, containing many small neurons (20 μm in diameter). [ 3H]Thymidine labelling of the transplants and intact cords of the surviving littermates of the donor fetuses suggested that these myelin-free areas corresponded to the substantia gelatinosa of the adult spinal cord. In many cases, the transplants were confluent with the host CNS parenchyma without an intervening glial scar. Furthermore, multiple spinal cord transplants, placed into the same lesion site, were often fused, and injection of one of the transplants with horseradish peroxidase demonstrated many retrogradely labelled neurons in the adjacent implant. The results of this study suggest that some topographical features of the normal spinal cord may be represented in mature spinal cord transplants. In addition, these findings establish a basis for future investigations aimed at repair of the injured host spinal cord with homologous fetal tissue.