Lineage Reprogramming A Promising Road for Pancreatic β Cell Regeneration

Cell replacement therapy is a promising method to restore pancreatic beta 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 beta cells in vitro and in vivo. However, while some reprogrammed beta cells bear similarities to bona fide beta cells, others do not develop into fully functional beta cells. Here we review various strategies currently used for beta 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 beta cells suitable for cell replacement therapy.