The role of embryonic motoneuron transplants to restore the lost motor function of the injured spinal cord.

Spinal cord injury or disease result in the loss of critical numbers of spinal motoneurons and consequentially, in severe functional impairment. The most successful way to replace missing motoneurons is the use of embryonic postmitotic motoneuron grafts. This method may also at least partially restore integrity of the injured spinal cord. It has been shown that grafted motoneurons survive, differentiate and integrate into the host cord and many of them are able to reinnervate the denervated muscles. If grafted motoneurons are provided with a conduit (e.g. reimplanted ventral root) the grafted cells are able to extend their axons along the entire length of the peripheral nerves and reach the hind or forelimb muscles and to restore limb locomotion patterns. Grafted motoneurons show excellent survival in motoneuron-depleted adult host cords, but the developing spinal cord appears to provide an unfavourable environment for these motoneurons as they do not survive in immature cords. The long term survival and maturation of the grafted neurons depend on the availability of a nerve conduit and one or more target muscles, independently of whether these are ectopic nerve-muscle implants or limb muscles in their original site. Thus, grafted and host motoneurons induce functional recovery in the denervated limb muscles when their axons can grow into an avulsed and reimplanted ventral root and then reach the limb muscles. Following segmental loss of motoneurons induced by partial spinal cord injury, motoneuron-enriched embryonic grafts can be placed into the gap-like hemisection cavity in the cervical spinal cord. Such transplants induce the regeneration of great numbers of host motoneurons possibly by the bridging effect of the grafts. In this case, the regenerating host motoneurons reinnervate their original target muscles while the small graft plays a minimal role in the reinnervation of muscles. These results suggest that reconstruction of the injured spinal cord using an embryonic motoneuron-enriched spinal cord graft is a feasible way to achieve improvement after severe functional motor deficits of the spinal cord.