Year 3

Since the beginning of this project, we report considerable progress toward our aims of investigating the safety and efficacy of human inhibitory nerve precursor (MGE) cell transplantation for the treatment of spinal cord injury-induced bladder spasticity and neuropathic pain. In year one of this award we completed the major objectives of Aim1, namely to explore the survival, integration, and cell fate of stem cell-derived MGE cell transplants in the uninjured rodent spinal cord. We have now obtained preliminary efficacy results from Aim 2, namely the effects of hESC-MGE cells injected in spinal cord injured animals. Behavioral testing has been obtained to assess pain thresholds for all injected animals up to the six month endpoint, and measures of bladder spasticity have been obtained at six months post cell injection. We have now evaluated the unblinded data and find that it demonstrates amelioration of neuropathic pain and bladder spasticity. Our histological analysis shows robust human cell survival, distribution, and neuronal differentiation, and we have electrophysiological data indicating functional integration of the transplanted cells. We are preparing a manuscript for publication.