Reprogramming of pancreatic islet cells for regeneration and rejuvenation.

The pancreatic ß cell, which produces insulin, is a terminally differentiated cell type that divides rarely. Consequently, the regenerative ability of ß cells is limited and irreversible diabetes occurs after severe loss of ß-cell function. In view of such poor regenerative capacity, considerable research efforts have been made to promote the expansion of functional insulin-producing cells as a regenerative therapy for diabetes. Here, we discuss recent findings regarding the robust expansion of functional mature islet cells both in vivo and ex vivo through MYCL-mediated reprogramming. We also describe the potential prospects for the application of reprogramming technologies to regenerative therapy and rejuvenation of islet cells.

MYCL-mediated reprogramming expands pancreatic insulin-producing cells.

ß cells have a limited capacity for regeneration, which predisposes towards diabetes. Here, we show that, of the MYC family members, Mycl plays a key role in proliferation of pancreatic endocrine cells. Genetic ablation of Mycl causes a reduction in the proliferation of pancreatic endocrine cells in neonatal mice. By contrast, the expression of Mycl in adult mice stimulates the proliferation of ß and α cells, and the cells persist after withdrawal of Mycl expression. A subset of the expanded α cells give rise to insulin-producing cells after this withdrawal. Transient Mycl expression in vivo is sufficient to normalize the hyperglycaemia of diabetic mice. In vitro expression of Mycl similarly provokes active replication in islet cells, even in those from aged mice. Finally, we show that MYCL stimulates the division of human adult cadaveric islet cells. Our results demonstrate that the induction of Mycl alone expands the functional ß-cell population, which may provide a regenerative strategy for ß cells.