Primate models in organ transplantation

Abstract

Large animal models have long served as the proving grounds for advances in transplantation, bridging the gap between inbred mouse experimentation and human clinical trials. Although a variety of species have been and continue to be used, the emergence of highly targeted biologic- and antibody-based therapies has required models to have a high degree of homology with humans. Thus, the nonhuman primate has become the model of choice in many settings. This article will provide an overview of nonhuman primate models of transplantation. Issues of primate genetics and care will be introduced, and a brief overview of technical aspects for various transplant models will be discussed. Finally, several prominent immunosuppressive and tolerance strategies used in primates will be reviewed.

Figure 1.

Primate renal transplantation. (A) A retroperitoneal pocket is created starting medial to the native ureter and moving laterally. (B) The donor vessels are anastomosed to the recipient vena cava and aorta. (C) Following reperfusion, the donor ureter is tunneled through the retroperitoneum to a posterior cystotomy and anchored within the bladder.

Figure 2.

NHP skin grafts. In the upper panel, grafts have been sewn in place and anchor sutures placed. The sutures are left long so that they can be used to affix cotton bolsters over the grafts to stabilize the grafts for approximately 1 week. In the lower panel, the grafts are shown after having healed to the underlying tissue. Note that the allografts are undergoing early rejection and appear erythematous when compared with the autografts.

Figure 3.

Radial forearm vascularized composite allotransplantation (VCA) containing bone, muscle, tendon, nerve, vasculature, subcutaneous fat, and skin. (From Cendales et al. 2005; reprinted, with express permission, from the author.)