Pancreatic regeneration: role of pancreatic progenitors

Abstract

The regenerative process in the pancreas is of particular interest since diabetes, whether type 1 or type 2, results from an inadequate amount of insulin‐producing β‐cells. The presence of pancreatic stem/progenitor cells has been suggested by the observation of islet neogenesis, the formation of new islets seen as budding of hormone positive cells from the ductal epithelium. Our data from the regeneration rat model of partial pancreatectomy led us to hypothesize that differentiated pancreatic ductal cells were the pancreatic progenitors after birth, that with replication they regressed to a less differentiated phenotype and then could differentiate to form new acini and islets. To test this hypothesis, we took a direct approach of genetically marking ductal cells using carbonic anhydrase II (CAII) as a duct cell‐specific promoter to drive cre recombinase in Cre‐lox lineage tracing experiments. We show that CAII‐expressing pancreatic cells act as progenitors that give rise to both new islets and acini after birth and after injury (ductal ligation). It is still unclear if all, or only a subpopulation, of the ductal cells have this potential. This identification of an in vivo progenitor for all differentiated pancreatic cell types has implications for a potential expandable source for new islets for replenishment therapy for diabetes either in vivo or ex vivo.