Researchers successfully expanded and differentiated human pancreatic duct tissue into islet-like cells in vitro, offering a potential new source of insulin-producing cells for diabetes treatment. The study used discarded ductal tissue from eight islet isolations and cultured it under conditions that allowed ductal cells to form three-dimensional structures, from which islet-like clusters (CHIBs) budded. Over 3–4 weeks, the insulin content increased 10–15-fold, while DNA content increased up to 7-fold. The CHIBs contained cytokeratin 19-positive duct cells and hormone-positive islet cells, with some cells showing immature differentiation. Insulin secretion studies showed a 2.3-fold increase in insulin secretion in response to 20 mM glucose compared to 5 mM glucose. This suggests that duct tissue can be expanded and directed to differentiate into glucose-responsive islet tissue in vitro. The study highlights the potential of this approach for generating new islet cells for transplantation, addressing the shortage of donor islets. The findings indicate that ductal cells can be expanded and differentiated into islet cells, with the potential for future optimization to increase yields for clinical use. The research provides evidence that ductal cells can be transformed into islet cells, which could be used for β-cell replacement therapy in diabetes patients. The study also discusses the limitations of current islet transplantation and the potential of this new method to improve the availability of islet cells for treatment. The results suggest that ductal tissue can be used to generate islet-like cells, which could be a promising alternative to traditional islet transplantation. The study emphasizes the importance of further research to optimize the process and improve the efficiency of islet cell generation.Researchers successfully expanded and differentiated human pancreatic duct tissue into islet-like cells in vitro, offering a potential new source of insulin-producing cells for diabetes treatment. The study used discarded ductal tissue from eight islet isolations and cultured it under conditions that allowed ductal cells to form three-dimensional structures, from which islet-like clusters (CHIBs) budded. Over 3–4 weeks, the insulin content increased 10–15-fold, while DNA content increased up to 7-fold. The CHIBs contained cytokeratin 19-positive duct cells and hormone-positive islet cells, with some cells showing immature differentiation. Insulin secretion studies showed a 2.3-fold increase in insulin secretion in response to 20 mM glucose compared to 5 mM glucose. This suggests that duct tissue can be expanded and directed to differentiate into glucose-responsive islet tissue in vitro. The study highlights the potential of this approach for generating new islet cells for transplantation, addressing the shortage of donor islets. The findings indicate that ductal cells can be expanded and differentiated into islet cells, with the potential for future optimization to increase yields for clinical use. The research provides evidence that ductal cells can be transformed into islet cells, which could be used for β-cell replacement therapy in diabetes patients. The study also discusses the limitations of current islet transplantation and the potential of this new method to improve the availability of islet cells for treatment. The results suggest that ductal tissue can be used to generate islet-like cells, which could be a promising alternative to traditional islet transplantation. The study emphasizes the importance of further research to optimize the process and improve the efficiency of islet cell generation.