Transient cytokine treatment induces acinar cell reprogramming and regenerates functional beta cell mass in diabetic mice

The regenerative potential of terminally differentiated cells in mammals remains poorly understood. Unveiling signaling pathways responsible for activation of cellular plasticity might allow major advances in regenerative medicine. Pancreas non-beta cells, that remain unaffected by prior diabetogenic attacks, could provide an alternative therapy for diabetes if reprogrammed to functional beta-like cells. The present study provides proof of concept by demonstrating that administration of Epidermal Growth Factor (EGF) and Ciliary Neurotrophic Factor (CNTF) to adult mice with chronic hyperglycemia efficiently stimulates the conversion of terminally differentiated acinar cells to beta-like cells. Newly generated beta-like cells are able to restore a functional cell pool that reinstates normal glycemic control. The regenerative process depends on Stat3 signaling and expression of Neurogenin 3 (Ngn3) in acinar cells. These findings challenge the current opinion on cellular plasticity in the diabetic pancreas and might provide the biological basis for a novel therapeutic approach.

Jaar van publicatie:2014

Trefwoorden:endocrine pancreas, acinar cell, neurogenin 3, cell reprogramming, beta cell, diabetes

Toegankelijkheid:Closed