Pancreatic β-cell regeneration: Facultative or dedicated progenitors?

The adult pancreas is only capable of limited regeneration. Unlike highly regenerative tissues such as the skin, intestinal crypts and hematopoietic system, no dedicated adult stem cells or stem cell niche have so far been identified within the adult pancreas. New beta cells have been shown to form in the adult pancreas, in response to high physiological demand or experimental beta-cell ablation, mostly by replication of existing beta cells. The possibility that new beta cells are formed from other sources is currently a point of major controversy. Under particular injury conditions, fully differentiated pancreatic duct and acinar cells have been shown to dedifferentiate into a progenitor-like state, however the extent, to which ductal, acinar or other endocrine cells contribute to restoring pancreatic beta-cell mass remains to be resolved. In this review we focus on regenerative events in the pancreas with emphasis on the restoration of beta-cell mass. We present an overview of regenerative responses noted within the different pancreatic lineages, following injury. We also highlight the intrinsic plasticity of the adult pancreas that allows for inter conversion of fully differentiated pancreatic lineages through manipulation of few genes or growth factors. Taken together, evidence from a number of studies suggest that differentiated pancreatic lineages could act as facultative progenitor cells, but the extent to which these contribute to beta-cell regeneration in vivo is still a matter of contention. (C) 2016 Published by Elsevier Ireland Ltd.