Tolerance Protocols in Large Animal VCA Models—Comprehensive Review

Abstract

The clinical application of vascularized composite allografts (VCA) has continue to expand each year as new transplants are performed. However, chronic rejection and the many side effects from chronic immunosuppression continue to inhibit widespread application of VCA. Immune tolerance to VCA would address these two issues and shift the risk-benefit ratio to allow for the more widespread application of these transplants. Future development of clinical tolerance protocols will be generated from pre-clinical experiments performed in large animal models. This article reviews the current state of large animal tolerance protocols published for VCA. The most successful tolerance protocols thus far include the use of hematopoietic stem cell transplant with non-myeloablative preconditioning and establishment of donor cell chimerism. In addition to this strategy, several groups have examined the inclusion of mesenchymal and adipose-derived stem cells to address the complications related to the use of hematopoietic stem cell transplant (such as graft versus host disease). These large animal models are critical to development of a viable pre-clinical model for tolerance in vascularized composite allografts that can deliver a tolerant state with minimal harm to the recipient of these non-life-saving transplants.