Overcoming Immunobiological Barriers Against Porcine Islet Xenografts: What Should Be Done?

Porcine islets might represent an ideal solution to the severe shortage of living donor islets available for transplantation and thus have great potential for the treatment of diabetes. Although tremendous progress has been achieved through recent experiments, the immune response remains a major obstacle. This review first describes the 3 major pathways of rejection: hyperacute rejection mediated by preformed natural antibodies and complement, instant blood-mediated inflammatory reactions, and acute cell-mediated rejection. Furthermore, this review examines immune-related strategies, including major advances, which have been shown to extend the life and/or function of porcine islets in vitro and in vivo: (1) genetic modification to make porcine islets more compatible with the recipient, (2) optimization of the newly defined biological agents that have been shown to promote long-term survival of xenografts in nonhuman primates, and (3) development of novel immunoisolation technologies that maintain the long-term survival of islet xenografts without the use of systemic immunosuppressive drugs. Finally, the clinical application of porcine islet transplantation is presented. Even though less clinical information is available, experimental data indicate that porcine islet xenografts are likely to become a standard treatment for patients with type 1 diabetes in the future.