Pancreatic Ductal Cell Heterogeneity: Insights into the Potential for β-Cell Regeneration in Diabetes

Diabetes mellitus is a significant and fast-growing health problem worldwide. Cost, donor shortages, and immune rejection limit current treatment strategies. While considerable progress has been made in creating beta-cells in vitro with remarkable morphological and functional resemblance to those in primary pancreatic islets, exploring alternative sources for beta-cell replacement is crucial. With adult pancreatic stem cells still not conclusively identified, researchers focus their attention on heterogeneity within pancreatic ductal epithelial cells, exploring these cells as a potential source of progenitor cells for pancreatic regeneration and beta-cell formation. Recent studies using techniques such as fluorescence-activated cell sorting, immunostaining and single cell RNA-sequencing have identified ductal cell heterogeneity with several subpopulations of ductal cells with progenitor-like properties and their capacity for differentiation into insulin producing cells. Here, we have reviewed the most recent studies on pancreatic ductal cell subpopulations that offer insights into potential stem-cell populations to form beta-cells in diabetes treatment.