In vitro Directed Differentiation of Functional Pancreatic β Cells from Human Induced Pluripotent Stem Cells
Type 1 diabetes is caused by impaired function of pancreatic β-cells and insufficient insulin secretion.Currently,it is primarily managed with exogenous insulin supplementation;however,exogenous insulin cannot precisely regulate blood glucose levels,and severe hypoglycemia can be life-threatening.Islet transplantation serves as an alternative therapy,but faces challenges such as a shortage of organ donors and the risk of cross-species infections from xenogeneic sources of islet β-cells.Thus,obtaining a sufficient and safe supply of islet β-cells remains a significant challenge in cell therapy for type 1 diabetes.This study aims to differentiate human induced pluripotent stem cells(hiPSCs)into isletβ-cells in vitro,offering a potential new strategy for treating type 1 diabetes.To achieve this,we utilized a differentiation strategy that combines 2D and 3D culture systems to simulate the in vivo developmental environment of islet β-cells and employed various growth factors to regulate key signaling pathways crucial in pancreatic development and β-cell differentiation,including the Notch,Wnt,and TGF-β/Smad signaling pathways.Our results show that under combined 2D and 3D culture conditions,the expression of specific genes at the stages of definitive endoderm,pancreatic progenitors,pancreatic endocrine cells,and islet β-cells significantly increased(P＜0.05).And there was a marked enhancement in insulin content and secretion following glucose stimulation(P＜0.05).In summary,this study successfully established a differentiation strategy from hiPSCs to functional islet β-cells,providing a new cell therapy approach for type 1 diabetes.This method not only offers new tools for studying the developmental biology of islet β-cells,but also provides a potential source of islet β-cells for clinical applications,potentially overcoming the limitations of current treatment methods.
human induced pluripotent stem cells(hiPSCs)in vitro differentiationpancreatic beta cellsinsulin
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