Pancreatic acinar-to-beta cell transdifferentiation in vitro

Although accumulating evidence indicates that proliferation of pre-existing beta-cells is the major mechanism of the maintenance of postnatal beta-cell mass, new beta-cells can be generated from non-beta-cells under certain conditions in vitro. We have recently shown directly by Cre/loxP-based cell lineage tracing that adult mouse pancreatic acinar cells can be transdifferentiated into insulin-secreting cells in vitro. These newly made cells secrete insulin in response to glucose and other secretagogues, but their secretory capacity is still low compared to that of native beta-cells. To improve the efficiency of generation of insulin-secreting cells from non-beta cells, it is critical to understand the molecular mechanism of such transdifferentiation. Since pancreatic acinar cells are the most abundant cell type in the pancreas, their utilization as a source of surrogate beta-cells is an intriguing approach to cell replacement therapy for type 1 diabetes. This review focuses on current knowledge of the regeneration of pancreatic beta-cells and transdifferentiation of pancreatic acinar-cells into insulin-secreting cells.