Neuroprotection and Axonal Regeneration After Lumbar Ventral Root Avulsion by Re-implantation and Mesenchymal Stem Cells Transplant Combined Therapy

Ventral spinal root avulsion causes complete denervation of muscles in the limb and also progressive death of segmental motoneurons (MN) leading to permanent paralysis. The chances for functional recovery after ventral root avulsion are very poor owing to the loss of avulsed neurons and the long distance that surviving neurons have to re-grow axons from the spinal cord to the corresponding targets. Following unilateral avulsion of L4, L5 and L6 spinal roots in adult rats, we performed an intraspinal transplant of mesenchymal stem cells (MSC) and surgical re-implantation of the avulsed roots. Four weeks after avulsion the survival of MN in the MSC-treated animals was significantly higher than in vehicle-injected rats (45% vs. 28%). Re-implantation of the avulsed roots in the injured spinal cord allowed the regeneration of motor axons. By combining root re-implantation and MSC transplant the number of surviving MN at 28 days post-injury was higher (60%) than in re-implantation alone animals (46%). Electromyographic tests showed evidence of functional re-innervation of anterior tibialis and gastrocnemius muscles by the regenerated motor axons only in rats with the combined treatment. These results indicate that MSC are helpful in enhancing neuronal survival and increased the regenerative growth of injured axons. Surgical re-implantation and MSC grafting combined had a synergic neuroprotective effect on MN and on axonal regeneration and muscle re-innervation after spinal root avulsion.