Pancreatic Duct Cells as a Potential Source for Human Islet Neogenesis: Insights from Imaging Mass Cytometry

Abstract The question of whether islet neogenesis occurs in adult humans has been a subject of long-standing debate. To explore the characteristics of islet endocrine cells associated with pancreatic ducts, we employed imaging mass cytometry to examine pancreatic tissues from individuals across different age groups, including those with prediabetes or type 2 diabetes (T2D). Our analysis revealed the presence of all five pancreatic islet endocrine cell types, along with two types of non-hormone-expressing endocrine cells, located within or immediately adjacent to the ducts. These cells were most abundant in infancy, with a gradual decline observed through adulthood. Notably, ductal β cells predominated in infancy, whereas ductal α cells became more prevalent in adulthood, and significantly increased in the group aged over 60 years. Obesity further increased the ductal β cells in the subjects aged over 60 years. Under prediabetic and T2D conditions, an increase in all duct-related endocrine cells was observed. These findings indicate that ductal cells may serve as a reservoir for new pancreatic endocrine cells, offering potential insights into the promotion of endogenous β cell regeneration in diabetic patients. Highlights ◯ Characterization of various islet endocrine cell types related to ducts in human pancreas. ◯ The insulin-positive cells are the dominant cells among all duct-related islet endocrine cell types during the infancy period, however, the glucagon-positive cells become the dominant cells in adulthood. ◯ T2D, Obesity, and aging are involved in the increase in the number of duct-related endocrine cells.