Restore Synaptic Connectivity of Injured Spinal Cord with Human Embryonic Neurons

点击翻译按钮获取中文摘要

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. PUBLIC HEALTH RELEVANCE: Spinal Cord Injury (SCI) is damage to the spinal cord that results in permanent loss of function such as mobility or feeling below injury. There are approximately 250,000 Americans living with spinal cord injuries, and approximately 20,000 of those injured are veterans (data from Paralyzed Veterans of America). The number of such injuries is increasing as a result of the Iraq and Afghanistan war. Thus, care and treatment of spinal cord injured veterans is important to the VA patient care mission. The use of neural stem cells or progenitors as a functional relay is a very promised experimental study. Results from the current proposal will provide important knowledge that could form the basis for generating future therapies for acute and chronic SCI.