Posted July 9, 2013
W.P. Andrew Lee, M.D., Gerald Brandacher, M.D., Johns Hopkins University School of Medicine, Baltimore, Maryland
Current treatment options for severe combat wounds including nerve grafts, nerve transfers, and synthetic nerve conduits are limited by the wide zone of injury, large nerve gaps, and lack of available non-damaged nerves. In the past decade, over 100 different composite tissue allotransplantation (CTA) procedures have been performed around the world, including approximately 80 hand and 24 facial transplants, with encouraging graft survival and excellent functional outcomes. CTA has not been more widely utilized due to the strong immunorejection by the body, which requires long-term immunosuppression via high-doses of multiple anti-rejection drugs. Dr. Lee and Dr. Brandacher at Johns Hopkins University believe that an improved therapy could be utilized using a type of the patient's own adult stem cells that are present in multiple tissues called mesenchymal stem cells (MSCs). (The CTA teams at Johns Hopkins and University of Pittsburgh, directed by Dr. Lee, were the first to perform a double hand transplant and an entire forearm transplant in the United States.) MSCs have already been shown to suppress the immune system in specific ways that are related to rejection while minimizing nonspecific immunosuppression that could cause other complications.
Using funding from a Fiscal Year 2009 Peer Reviewed Orthopaedic Research Program Hypothesis Development Award, Dr. Lee and Dr. Brandacher examined MSC therapy in an animal model and demonstrated that local or systemic injections of the subject's own bone marrow-derived MSCs (BM-MSCs) significantly enhanced functional recovery and improved nerve regeneration following hind limb transplants. They found that MSCs possess potent immunomodulatory properties with minimal immunogenicity in vitro and that MSCs obtained from adipose (fat) tissue exhibited superior immunomodulatory properties compared to BM-MSCs. Dr. Lee and his team hope that MSC therapy can be developed further to enhance the regeneration of nerves as well as provide immunomodulation following CTA.