[Reprogramming of adult human pancreatic duct cells as functional beta cells]

The most plausible therapy for type I diabetes is restoration of the functional beta cell mass, as is proven by the clinical success of transplantation of donor beta cells. This approach, however, is very limited by the low number of donor organs available. One solution for this shortage would be well controlled generation of beta cells for transplantation. The bona fide beta progenitor cell is not known yet. As duct cells of the adult human pancreas show a high degree of plasticity, they were genetically manipulated to transdifferentiate into beta cells. The transcription factor neurogenin 3, a master switch of embryogenesis of the endocrine pancreas, was ectopically expressed in adult human pancreatic duct cells. Neurogenin 3 induced a phenotypic shift by activation of a series of endocrine marker genes, among which insulin. However, the number of insulin-producing cells and the amount of insulin per cell were low and the transdifferentiated duct cells remained glucose insensitive. A strategy for optimizing the reprogramming of adult human duct cells to beta cells is proposed.