Abstract
Diabetes is a complex disease that affects over 400 million people worldwide. The life-long insulin injections and continuous blood glucose monitoring required in type 1 diabetes (T1D) represent a tremendous clinical and economic burdens that urges the need for a medical solution. Pancreatic islet transplantation holds great promise in the treatment of T1D; however, the difficulty in regulating post-transplantation immune reactions to avoid both allogenic and autoimmune graft rejection represent a bottleneck in the field of islet transplantation. Cell replacement strategies have been performed in hepatic, intramuscular, omentum, and subcutaneous sites, and have been performed in both animal models and human patients. However more optimal transplantation sites and methods of improving islet graft survival are needed to successfully translate these studies to a clinical relevant therapy. In this review, we summarize the current progress in the field as well as methods and sites of islet transplantation, including stem cell-derived functional human islets. We also discuss the contribution of immune cells, vessel formation, extracellular matrix, and nutritional supply on islet graft survival. Developing new transplantation sites with emerging technologies to improve islet graft survival and simplify immune regulation will greatly benefit the future success of islet cell therapy in the treatment of diabetes.
Highlights
Diabetes is a complex metabolic disease in which the body’s ability to produce or respond to insulin is impaired, resulting in hyperglycemia
We have demonstrated that stem cell-derived pancreatic organoids that are capable of secreting insulin in response to varying glucose concentration but are immune evasive by modulating PD-L1 expression [43]
Current advances the field of islet transplantation for the treatment of diabetes focus on investigating the microenvironment of transplantation sites, including their vascularization, extracellular matrix content, and tissueresident immune cells
Summary
Diabetes is a complex metabolic disease in which the body’s ability to produce or respond to insulin is impaired, resulting in hyperglycemia. Non-fasting blood glucose level was not reported in minipigs, but retrieved device exhibited more surviving islets than controls after 1 and 2 months of implantation The islets with the vasculogenic hydrogel transplanted into the epididymal fat pad achieved normoglycemia within two weeks, for more than 35 days up to 100 days (approximately 75% of recipients)
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