Grants We Funded

Abstract
Composite tissue allotransplantation (CTA) presents a viable option for reconstructing difficult defects resulting from traumatic injury, congenital deformities, and surgical extirpation, CTA offers the advantage of providing an intact, preserved graft without donor site morbidity. A hand transplant is superior to a prosthetic only, in that recovery of sensation and precise neuromuscular function. Similarly, a face transplant is simply a mask if there is no ability for facial expression, sensation, and oral consumption. The overall goal of the proposed research is to improve sensory recovery after CTA through targeting the somatosensory cortex. Central nervous system modulations are key to optimizing sensory recovery after CTA. At the laboratory of W.P. Andrew Lee at the University of Pittsburgh in the Starzl Institute for Transplantation laboratory, preliminary experiments focused on defining changes in somatosensory cortical mapping and neuronal response properties after face transplantation in a rat model. Using electrophysiology, it was found that there n as cortical reintegration of sensory inputs, and thus reinnervation, after CTA. However, there are substantial changes in the pattern of sensory reinnervation in gene mapping from the periphery to the somatosensory cortex. The focus of the current research is therefore to investigate therapeutic interventions to enhance cortical functional restitution after CTA. Therapeutic strategies that mitigate central nervous system remodeling after CTA ultimately will help to improve functional recovery. Cytokines that mediate peripheral and central nervous system modulations that occur after injury may provide means to improve reinnervation and cortical reintegration after CTA. One such cytokine is Erythropoietin (Epo), a naturally occurring cytokine that initiates erythropoiesis. In addition to its hematopoietic effects, it has shown tissue protective activity in both the central nervous system (CNS) and peripheral nervous system (PNS) in vivo. Carbamylated Erythropoietin (Cepo), a synthetic polypeptide represents the prototype of a designer cytokine for therapeutic intervention in central and peripheral nervous system injury without erythropoietin side effects. The specific aim of the proposed study is to investigate the potential for the novel therapy, Cepo, to mitigate central nervous system changes that occur after composite tissue allotransplantation.