Opportunities and impediments of human pluripotent stem cell-derived islets in the treatment of diabetes

Abstract

Progress in human pluripotent stem cells has opened up an opportunity to autologous β-cell replacement therapies in patients with diabetes. Such an approach could render immunologically compatible islets from an unconstrained source without requirement for chronic immune suppression. Several proof-of-concept studies have generated stem cell-derived islets (SC-islets) capable of reversing diabetes in rodents and with similar functional characteristics to human donor islets. Autologous SC-islets offer potential to improve the life of patients living with diabetes by enabling cell replacement therapy that provides physiologic glycemic control with less risk to the recipient. Such efforts are impeded from ongoing challenges in scalability, latent potential for teratogenicity, an inability to fully recapitulate metabolic responses observed with primary islets, and protection from autoimmune recurrence in the setting of Type 1 diabetes. In this review, we outline potential opportunities and impediments for successful clinical translation of SC-islets as an effective therapy for patients with all forms of diabetes. We discuss recent advancements in scale-up manufacturing, the promise of gene-editing for optimized cellular protection, and methods to deliver safe and immune shielded cells to improve engraftment and survival. Finally, we discuss in detail goals and challenges in islet bioengineering and emphasize the need for improved methods to overcome the roadblocks in translating autologous SC-islet cell therapies to the clinic.