Use of Large-Animal and Nonhuman Primate Models for Reconstructive Transplantation

Abstract

The reports of the successful transplantation of vascularized composite allografts (VCA) to restore lost hands and damaged faces demonstrate the clinical impact of the emerging field of reconstructive transplantation. However, the growth of the field is limited by the need to use chronic immunosuppression to maintain these transplants. The development of protocols to induce tolerance to VCA is critical to the future of reconstructive transplantation. The development of the new strategies to reduce or eliminate the need for long-term immunosuppression currently relies on the use of animal models. Small-animal models have been a mainstay of transplantation research and play an important part in the development of a preclinical protocol. These models allow the exploration of multiple variations in a single protocol. However, results derived from small-animal models have not translated directly to the clinic. In fact, these protocols often fail even when applied to large-animal models. In this chapter, we examine the critical results and key limitations of small-animal models in VCA research. We explore the relative strengths and weaknesses of three large-animal models (nonhuman primates, swine, and canines) currently used in VCA research. Finally, we review the recent experimental findings and discuss the importance of the use of large-animal models to develop clinically relevant protocols for VCA transplantation.