Designing next-generation islet-like cells from human pluripotent stem cells: Advances in overcoming allorejection and recurrent type 1 diabetes

Although it is now possible to generate functional pancreatic islet-like cells from human pluripotent stem cells (hPSC-islets) in vitro, their ability to survive and function in immunocompetent hosts remains a major barrier to their clinical translation. While immunosuppression remains the gold standard for preventing allorejection in recipients of solid organ and hematopoietic stem cell transplantation, this approach comes with considerable toxicity that can limit the therapeutic benefit of cell therapy. In this brief review, we will examine the major types of immunologic rejection expected to affect hPSC-islets along with recent efforts to overcome this issue. In particular, we will review the use of HLA editing, PD-L1 overexpression, and encapsulation, on the prevention of allorejection and recurrent Type 1 Diabetes.