UCLA

Following a severe spinal cord injury (SCI), transplanted olfactory ensheathing cells (OECs) reduce inhibitory factors and promote axonal outgrowth at the lesion site to help reestablish circuit connectivity needed for functional recovery. Another promising therapy, electrical epidural stimulation (EES), also helps to reestablish connectivity but targets the spinal cord caudal to the injury. This study asked if the combination of OEC transplantation and administration of EES during climb training would improve recovery. Two cohorts of inbred Fischer 344 rats received a severe SCI and a two-week delayed transplant of OECs, media, or fibroblasts (FBs). Rats then received EES while performing a climbing task 3 times/week and were perfused at 5.5-6.5 months post-injury. We found that scores on the BBB locomotor test improved for all groups over time, but no consistent changes in climbing ability were detected. When we examined the injury sites, we found surviving GFP-labeled OECs and FBs for the first time at 6 months post-transplant. We also found that OEC treatment increased the amount of serotonergic and neurofilament (NF)-positive axons in the lesion core compared to media- and FB-treated controls. This was particularly true in areas of the lesion core with OECs where we found greater levels of axon density than in areas without OECs. Further, the percent of NF-positive axons associated with myelin proteins was greater in OEC- compared to media-treated rats. The OECs in the lesion core also interacted with serotonergic axons, myelinating and non-myelinating Schwann cells (SCs), and oligodendrocytes and expressed protein markers typically associated with SC-like myelin. Overall our results provide evidence that OEC transplantation combined with EES may be a beneficial treatment for severe SCI.