Abstract
Insulin injection is currently the main therapy for type 1 diabetes (T1D) or late stage of severe type 2 diabetes (T2D). Human pancreatic islet transplantation confers a significant improvement in glycemic control and prevents life-threatening severe hypoglycemia in T1D patients. However, the shortage of cadaveric human islets limits their therapeutic potential. In addition, chronic immunosuppression, which is required to avoid rejection of transplanted islets, is associated with severe complications, such as an increased risk of malignancies and infections. Thus, there is a significant need for novel approaches to the large-scale generation of functional human islets protected from autoimmune rejection in order to ensure durable graft acceptance without immunosuppression. An important step in addressing this need is to strengthen our understanding of transplant immune tolerance mechanisms for both graft rejection and autoimmune rejection. Engineering of functional human pancreatic islets that can avoid attacks from host immune cells would provide an alternative safe resource for transplantation therapy. Human pluripotent stem cells (hPSCs) offer a potentially limitless supply of cells because of their self-renewal ability and pluripotency. Therefore, studying immune tolerance induction in hPSC-derived human pancreatic islets will directly contribute toward the goal of generating a functional cure for insulin-dependent diabetes. In this review, we will discuss the current progress in the immune protection of stem cell-derived islet cell therapy for treating diabetes.
Highlights
Diabetes is a complex disease that affects more than 30 million people in the US alone and over 463 million people worldwide
Immune-evasive human islets derived from Human pluripotent stem cells (hPSCs) represent a promising and renewable cell source with a reduced risk of chronic immune suppression to treat insulin-dependent diabetes
The manufacturing scalability of hPSC-derived b cells or islet organoids must be addressed before its widespread clinical application can become a reality
Summary
Diabetes is a complex disease that affects more than 30 million people in the US alone and over 463 million people worldwide. Mouse pancreatic islets cultured in 100 μM EGCG-containing medium and transplanted under the kidney capsules of STZ-induced diabetic mice demonstrated preserved insulin secretion and decreased ROS production as a function of the Nrf pathway [151] Taken together, these findings indicate multiple avenues for further studies focusing on pancreatic islet protection against inflammatory immune responses, hypoxia, and the transplant microenvironment. Because hiPSCs can be derived from adult tissues, they unlock a powerful form of personalized medicine: fibroblast cells taken from patients, converted into hiPSCs, and differentiated into pancreatic islet b cells could be transplanted autologously This practice reduces the risk of graft versus host disease by accounting for immune identity [158, 159]. Transcriptome analyses in MPS-HILOs revealed “de novo” anti-inflammatory gene induction by MPS [83]
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