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Tolerance in Nonhuman Primates by Delayed Mixed Chimerism

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Technical Report,15 Sep 2013,14 Sep 2017

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The Massachusetts General Hospital Boston United States

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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 of VCA and ultimately expand availability of these procedures to severely injured service men and women, and civilian victims of disabling and disfiguring trauma or disease. The objective of the VCA laboratory at the MGH 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 principle of delayed induction of mixed chimerism in a non-human primate NHP model. This approach, in contrast to protocols which have already reached clinical trials 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 for VCAs using this protocol in NHPs can be expected to lead to rapid translation into clinical trials.

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  • Medicine and Medical Research

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