UCLA

Olfactory ensheathing cells (OECs) are unique glia that support axon outgrowth in the olfactory system and have shown some success as a cellular transplant therapy for the recovery of sensorimotor control after spinal cord injury. A pilot study was designed in which 10 female Sprague-Dawley rats received acute transplantation of skin fibroblasts (FB, control, n=5) or OECs (n=5) after a complete mid-thoracic spinal cord transection. All rats were implanted with epidural stimulating electrodes at spinal cord levels L1 and S2 and trained to climb an inclined grid while receiving sub-threshold stimulation for 20 min., 3 times/week for 6 months. We injected the Bartha-152 (EGFP-expressing) strain of pseudorabies virus (PRV) into the soleus and/or tibialis anterior muscles 6 days before termination to identify hindlimb motor circuits and assess connectivity across the injury site. Viral transport to cholinergic somatic motor neurons and premotor interneurons was detected in 8 rats (4 FB, 4 OEC). Three rats (2 FB, 1 OEC) had evidence of viral labeling rostral to the transection site (T3-6), including cholinergic and Chx10-positive V2a interneurons. Serotonergic axons crossed from the rostral to the caudal stump on GFAP-positive astrocyte bridges in 2 of the 3 rats with evidence of PRVeGFP labeling above the injury site (1 FB, 1 OEC). Together these data imply that long-term axonal regeneration occurred in two of our complete spinal rats after epidural stimulation, climb training, and olfactory ensheathing cell or fibroblast transplantation.