Immune Response Associated with Islet Xenotransplantation in Small and Large Animal Models

Abstract

This chapter will review studies that examine the immune response to porcine neonatal pancreatic cell clusters (NPCC) in small and large animal models; specifically, the immune mechanisms that lead to the rejection of transplanted islet cells in mice, nonhuman primates, and humans will be discussed. In addition, current research on the in vitro and in vivo human immune responses to porcine NPCC is also included. Research into the immune responses that lead to islet cell death posttransplant allows for further understanding of how to better protect transplanted porcine NPCC in humans. Furthermore, this chapter will examine immune-related strategies that have shown to extend the life and/or function of porcine NPCC in vitro and in vivo, including techniques that work to modulate the immune system of the islet cell donor and/or the recipient. Finally, this chapter will identify future areas of research that have yet to be examined extensively in the literature, mostly pertaining to the human immune response to porcine NPCC in the clinical setting.

Engineering of hybrid spheroids of mesenchymal stem cells and drug depots for immunomodulating effect in islet xenotransplantation

“…A pancreatic rat-to-mouse islet xenotransplantation model was established to develop strong immune reactions ( 26 ). Islets [400 islet equivalents (IEQs)] were transplanted alone (control) or with RAP-MPs, non–RAP-MP spheroids, or hybrid spheroids under the kidney capsules of streptozocin (STZ)–rendered diabetic C57BL/6 mice (Fig.…”