Carbonic anhydrase II-positive pancreatic cells are progenitors for both endocrine and exocrine pancreas after birth

Akari Inada, Cameron Nienaber, Hitoshi Katsuta, Yoshio Fujitani, Jared Levine, Rina Morita, Arun Sharma, Susan Bonner-Weir

Research output: Contribution to journalArticlepeer-review

327 Citations (Scopus)

Abstract

The regenerative process in the pancreas is of particular interest because diabetes results from an inadequate number of insulin-producing beta cells and pancreatic cancer may arise from the uncontrolled growth of progenitor/stem cells. 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 preexisting differentiated cell types accounting for some replacement. Additionally, neogenesis or the budding of new islet cells from pancreatic ducts has been reported, but the existence and identity of a progenitor cell have been debated. We hypothesized that the progenitor cells are duct epithelial cells that after replication undergo a regression to a less differentiated state and then can 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 recombinase (Cre) or inducible CreER™ to cross with ROSA26 loxP-Stop-loxP LacZ reporter mice. 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 (ductal ligation). This identification of a differentiated pancreatic cell type as an in vivo progenitor of all differentiated pancreatic cell types has implications for a potential expandable source for new islets for replenishment therapy for diabetes.

Original languageEnglish
Pages (from-to)19915-19919
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume105
Issue number50
DOIs
Publication statusPublished - Dec 16 2008
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • General

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