Generation of Pancreatic beta-cells From iPSCs and their Potential for Type 1 Diabetes Mellitus Replacement Therapy and Modelling

摘要

Diabetes type 1 (T1D) is a common autoimmune disease characterized by permanent destruction of the insulin-secreting beta-cells in pancreatic islets, resulting in a deficiency of the glucose-lowering hormone insulin and persisting high blood glucose levels. Insulin has to be replaced by regular subcutaneous injections, and blood glucose level must be monitored due to the risk of hyperglycemia. Recently, transplantation of new pancreatic beta-cells into T1D patients has come to be considered one of the most potentially effective treatments for this disease. Therefore, much effort has focused on understanding the regulation of beta-cells. Induced pluripotent stem cells (iPSCs) represent a valuable source for T1D modelling and cell replacement therapy because of their ability to differentiate into all cell types in vitro. Recent advances in stem cell-based therapy and gene-editing tools have enabled the generation of functionally adult pancreatic beta-cells derived from iPSCs. Although animal and human pancreatic development and beta-cell physiology have significant differences, animal models represent an important tool in evaluating the therapeutic potential of iPSC-derived beta-cells on type 1 diabetes treatment. This review outlines the recent progress in iPSC-derived beta-cell differentiation methods, disease modelling, and future perspectives.