Transplantation of embryonic neurones to replace missing spinal motoneurones

Abstract

Loss of spinal motoneurones results in severe functional impairment. The most successful way to replace missing motoneurones is the use of embryonic postmitotic motoneurone grafts. It has been shown that grafted motoneurones survive, differentiate and integrate into the host cord. If grafted motoneurones are provided with a suitable conduit for axonal regeneration (e.g. a reimplanted ventral root) the grafted cells are able to grow their axons along the whole length of the peripheral nerves to reach muscles in the limb and restore function. Grafted motoneurones show excellent survival in motoneurone-depleted adult host cords, but the developing spinal cord appears to be an unfavourable environment for these cells. The long term survival and maturation of the grafted neurones are dependent on the availability of a nerve conduit and one or more target muscles, no matter whether these are ectopic nerve-muscle implants or limb muscles in their original place. Thus, grafted and host motoneurones induce functional recovery of the denervated limb muscles when their axons regenerate into an avulsed and reimplanted ventral root. On the other hand, motoneurone-enriched embryonic grafts placed into a hemisection cavity in the cervical spinal cord induce axonal regeneration from great numbers of host motoneurones, possibly by the bridging effect of the grafts. In this case the regenerating host motoneurones reinnervate their original target muscles while the graft provides few axons for the reinnervation of muscles. These results suggest that reconstruction of the injured spinal cord with embryonic motoneurone-enriched spinal cord graft is a feasible method to improve severe functional motor deficits.