Reinnervation of adult rat gastrocnemius muscle by embryonic motoneurons transplanted into the axotomized tibial nerve.

In some cases of spinal cord injury and in certain motoneuron diseases, such as amyotrophic lateral sclerosis and spinal muscular atrophies, lower motoneurons are destroyed and muscle function cannot be restored except by reinnervation from alternate motoneuron sources. We have tested the feasibility of employing local transplantation of embryonic motoneurons to restore innervation to denervated somatic muscle as a first step in salvaging muscle function and enabling use of functional electric stimulation. Dissociated ventral spinal cord cells from Embryonic Days 14 and 15 rats were transplanted into the distal stump of axotomized tibial nerves of adult rats. Animals were killed 3-18 weeks after transplantation. After 3 weeks large multipolar cells, resembling alpha motoneurons, were observed within the transplant site surrounded by myelinated and unmyelinated axons and dendrites. Axons emanating from these transplanted motoneurons were identified within the nerve stump and within the previously denervated gastrocnemius muscle, forming neuromuscular junctions. Transplanted motoneurons survived up to 18 weeks and were labeled after intramuscular injection of fast blue. This study demonstrates that embryonic spinal motoneurons, transplanted into the distal adult peripheral nerve stump, are able to survive and reinnervate the denervated target muscle. We are now exploring the possibility of using this experimental approach to retard the atrophy of denervated skeletal muscle, thus providing a muscle capable of useful response to functional electrical stimulation.