The type 1 diabetes immune niche: Immunomodulatory biomaterial design considerations for beta cell transplant therapies

Abstract

Islet transplantation is a promising therapy for a subset of people with Type 1 diabetes (T1D). However, beta cell transplant clinical trials have largely failed to maintain long-term normal glycemia in transplant recipients. This is broadly due to immune rejection of the transplanted islets themselves or the devices in which these cells are encapsulated. As an autoimmune condition, the T1D host presents a uniquely challenging immunological niche for the transplant of additional beta cells. An understanding of the autoimmune environment is crucial for the development of successful beta cell transplant therapies. Here, we provide an overview of the immune cell pathways leading to autoimmune T1D, and the resulting immune niche. Next, we examine biomaterial platforms that can be used for cell transplantation, and describe those that seek to modulate the immune environment to mitigate immune rejection. These approaches include delivery of localized immune cues, co-transplantation with immunomodulatory cells, strategies to engineer islets ex-vivo, and antigen-specific immunomodulation to generate operational tolerance. Finally, we describe therapies which seek to prevent T1D progression which could be repurposed to support beta cell transplantation and future immunoengineering design considerations for successful islet transplantation therapies.