Tolerance in Nonhuman Primates by Delayed Mixed Chimerism

: Vascularized composite allografts (VCA) are transplants containing multiple tissue types (including bone, muscle, skin, nerves and blood vessels), which offer patients restoration of function and form following severe, disabling and disfiguring injury or tissue loss, in circumstances where the results of conventional reconstructive surgery remain unsatisfactory. The high incidence of episodes of skin-targeted acute rejection, and the morbidity associated with current immunosuppression regimens, necessary throughout the life of the recipient to prevent rejection, remain significant areas in which improvement would enhance quality of life, improve the risk-benefit ratio and ultimately expand availability of these procedures to severely injured service men and women, and civilians victims of disabling and disfiguring trauma or disease (Leonard et al, 2013). The objective of the VCA laboratory at the TBRC is to develop a clinically-applicable strategy for the induction of immune tolerance of VCAs. The aim of the work supported by this award is to introduce and optimize a protocol for VCA tolerance based on the principal of delayed induction of mixed chimerism in a non-human primate model. This approach, in contrast to protocols which have already reached clinical trial for kidney transplantation, permits induction of tolerance in the context of transplantation from deceased donors a prerequisite for clinical application in VCA. Successful induction of tolerance of VCAs using this protocol in non-human primates can be expected to lead to rapid translation to clinical trial.