Restore Synaptic Connectivity of Injured Spinal Cord with Human Embryonic Neurons

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DESCRIPTION (provided by applicant): Pilot Project Summary Spinal cord injury (SCI) often damages not only white matter axon tracts that carry signals to and from the brain, but also the central gray matter, causing segmental losses of interneurons and motor neurons. Transplantation of neural stem cells or neural progenitors not only potentially replaces lost neurons and glia, but could also serve as a functional relay between spinal cord segments that are disconnected by injury. Our preliminary data provide strong support for this functional relay hypothesis, showing ingrowth of host axons into embryonic neurons grafted to sites of spinal cord injury, and remarkable emergence of grafted axons into the host spinal cord. More importantly, grafted embryonic neurons supported formation of functional electrophysiological relays across sites of complete spinal transection, resulting in behavioral recovery; spinal re-transection above the graft abolished all recovery. These findings indicate that embryonic neurons can serve as functional relays to restore functional synaptic connectivity after SCI. The purpose of this pilot project is to bring these findings to clinical practicality by determining whether human fetal spinal cord neurons, especially high proportion of excitatory interneurons, can form similar functional relays to restor locomotion activity after complete spinal cord transection in rat model. We collaborate with Neuralstem Inc. that provides the clinical grade of human fetal spinal cord neurons that are currently approved by FDA for clinical trial for treatment of amyotrophic lateral sclerosis (ALS). The successful of this Pilot Project could lead to a full Merit Review translational study. The goals of this research are directly and highly relevant to the VA patient care mission.