Lineage Reprogramming: A Promising Road for Pancreatic β Cell Regeneration

Cell replacement therapy is a promising method to restore pancreatic β cell function and cure diabetes. Distantly related cells (fibroblasts, keratinocytes, and muscle cells) and developmentally related cells (hepatocytes, gastrointestinal, and pancreatic exocrine cells) have been successfully reprogrammed into β cells in vitro and in vivo. However, while some reprogrammed β cells bear similarities to bona fide β cells, others do not develop into fully functional β cells. Here we review various strategies currently used for β cell reprogramming, including ectopic expression of specific transcription factors associated with islet development, repression of maintenance factors of host cells, regulation of epigenetic modifications, and microenvironmental changes. Development of simple and efficient reprogramming methods is a key priority for developing fully functional β cells suitable for cell replacement therapy.

TrendsReadily available cells, such as fibroblasts and blood cells, might be used for in vitro reprogramming into β cells in patient-specific transplantation.In vivo β cell reprogramming will potentially be an important strategy for β cell regeneration. At present, the leading cell contenders for successful therapeutic transformation into β cells appear to be pancreatic endocrine α cells, exocrine acinar cells, and enteroendocrine cells.For instructive strategies, complete small molecule-based reprogramming independent of gene manipulations will need to be extensively investigated with the goal to obtain fully functional β cells for clinical application.