MSC Therapy for Nerve Regeneration and Immunomodulation after Composite Tissue Allotransplantation

The views, opinions and/or findings contained in this report are those of the author(s) and should not be construed as an official Department of the Army position, policy or decision unless so designated by other documentation. Public reporting burden for this collection of information is estimated to average 1 hour per response, including the time for reviewing instructions, searching existing data sources, gathering and maintaining the data needed, and completing and reviewing this collection of information. Send comments regarding this burden estimate or any other aspect of this collection of information, including suggestions for reducing Respondents should be aware that notwithstanding any other provision of law, no person shall be subject to any penalty for failing to comply with a collection of information if it does not display a currently valid OMB control number. Composite Tissue Allotransplantation (CTA) offers an alternative reconstructive strategy for complicated musculoskeletal injuries incurred during modern warfare where functional outcomes after multiple conventional reconstructions are suboptimal. Broader clinical application of CTA, however, continues to be hampered by requirement for long-term multi-drug immunosuppression to prevent graft rejection. Furthermore, unlike in solid organs, clinical success is dictated not only by graft acceptance, but also by functional outcome. Our study proposes a novel cell-based therapy utilizing mesenchymal stem cells (MSC) that can augment nerve regeneration while minimizing the need for immunosuppression. After transition from University of Pittsburgh to Johns Hopkins University, we optimized our isolation and culture protocol for MSCs. Immunophenotypic and functional characterization of cultured cells demonstrated potent immunomodulatory effects of MSCs in vitro. Preliminary functional outcome analysis using Catwalk showed convergent data with similar loss and return of function among groups. Similarly, compound muscle action potentials at early time points showed small non-significant increases in amplitude in experimental groups. In contrast, normalized gastrocnemius weights showed increased muscle weight in only the systemic injection group. Overall, we continue to monitor both functional and histological outcomes. Consistent with existing literature on nerve regeneration, we expect to observe more evident differences among groups with increased data over the longer term. INTRODUCTION Composite Tissue Allotransplantation (CTA) is an innovative reconstructive modality that can provide functional restoration after complex musculoskeletal trauma such as upper extremity amputation or disfiguring facial trauma 1. CTA has provided new hope for service members suffering from catastrophic combat trauma. The implementation of cellular therapies that integrate the concepts of immune regulation with those of nerve regeneration can …