Investigator: Eric E. Sabelman, PhD Project Staff: Min Hu, MD, PhD and Adrian Cameron, PhD Project Category: Spinal Cord Injury - 2000 Purpose: The goal of this proposal is to adapt a multi-component artificial peripheral nerve graft (ANG) developed by VA Palo Alto Rehabilitation R&D Center for use in bridging traumatic lesions of the spinal cord, in collaboration with Immune Response Corporation (IRC), Carlsbad, CA. The ANG is composed of an outer sheath, an internal core matrix of oriented collagen fibers having a microarchitecture promoting axonal alignment, and cultured Schwann cells, similar to the composition of a peripheral nerve autograft. Our ANG has several advantages compared to other experimental methods for cellular transplantation into the spinal cord: (a) The graft is collagen-based rather than synthetic polymer-based; its enzyme-mediated mechanism of remodeling is the same as for natural tissues; (b) The internal core provides a framework for axons to grown a spatially oriented manner, increasing the number of axons that grow into the graft; (c) It can serve as a platform for the delivery of a variety of factors to the injured spinal cord, including antioxidants to counteract effects of inflammation, neurotrophins for attracting regenerating nerve fibers, plasmids for genetically altering cells that come into contact, and, potentially, neuron stem cells to replace cells killed by trauma. We will test the ANG in a rat spinal cord injury model, first without added cells, then with normal Schwann cells and with combinations of the above additives. This proposal represents the first step toward a possible Co-Operative Research and Development Agreement between the VA and the Immune Response Corporation (5935 Darwin Ct, Carlsbad, CA 92008; http://www.imnr.com), a biopharmaceutical company developing gene-based therapies to induce specific cell responses for treatment of cancer, autoimmune and other disorders. The collaboration between the VA Palo Alto Rehabilitation R&D Center and the Immune Response Corporation will combine their respective expertise in extracellular matrix microarchitecture and genomic and phenotypic manipulation of cells. The proposed study will test whether the tissue-engineered graft we have developed offers advantages over other methods of placing Schwann cells and bioactive agents into the injured spinal cord. Funding Source: Christopher Reeve Paralysis Foundation Funding Status: In Review |
