New islets Formation from Pancreatic Progenitor Cells after Birth

Abstract

Continued and substantial growth of islet tissue occurs after birth in rodents and humans, with additional compensatory growth in response to increased demand. In rodents there is clear evidence of pancreatic regeneration after some types of injury, with proliferation of pre-existing differentiated cell types accounting for some replacement. Additionally, neogenesis has been reported. However, the existence and identity of a progenitor cell has been debated. We hypothesized that the stem cells are duct epithelial cells that after replication undergo a regression to a less differentiated state and can then form new endocrine and exocrine pancreas. To directly test whether ductal cells serve as pancreatic progenitors after birth and give rise to new islets, we generated transgenic mice expressing human carbonic anhydrase II (CAII) promoter: Cre or inducible Cre-estrogen receptor to cross with ROSA beta geo26 (ROSA26) reporter mice (ROSA26-loxP-stop-loxP-lacZ; in the cells that Cre is expressed, loxP will be cut out and allows LacZ to be expressed). We show that CAII-expressing cells within the pancreas act as progenitors that give rise to both new islets and acini normally after birth and after injury.