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. Islet neogenesis, or the formation of new islets, seen as budding of hormone-positive cells from the ductal epithelium, has long been considered to be one of the mechanisms of normal islet growth after birth and in regeneration, and suggested the presence of pancreatic stem cells. Results from the rat regeneration model of partial pancreatectomy led us to hypothesize that differentiated pancreatic ductal cells were the pancreatic progenitors after birth, and that with replication they regressed to a less differentiated phenotype and then could differentiate to form new acini and islets. There are numerous supportive results for this hypothesis of neogenesis, including the ability of purified primary human ducts to form insulin-positive cells budding from ducts. However, to rigorously test this hypothesis, we took a direct approach of genetically marking ductal cells using CAII (carbonic anhydrase II) as a duct-cell-specific promoter to drive Cre recombinase in lineage-tracing experiments using the Cre-Lox system. 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). This identification of a differentiated pancreatic cell type as 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.
Skip Nav Destination
Article navigation
June 2008
- Cover Image
- PDF Icon PDF LinkFront Matter
- PDF Icon PDF LinkTable of Contents
Conference Article|
May 21 2008
Transdifferentiation of pancreatic ductal cells to endocrine β-cells
Susan Bonner-Weir;
Susan Bonner-Weir
1
1Joslin Diabetes Center and Harvard Medical School, 1 Joslin Place, Boston, MA 02215 U.S.A.
1To whom correspondence should be addressed (email Susan.Bonner-Weir@Joslin.Harvard.edu).
Search for other works by this author on:
Akari Inada;
Akari Inada
1Joslin Diabetes Center and Harvard Medical School, 1 Joslin Place, Boston, MA 02215 U.S.A.
Search for other works by this author on:
Shigeru Yatoh;
Shigeru Yatoh
1Joslin Diabetes Center and Harvard Medical School, 1 Joslin Place, Boston, MA 02215 U.S.A.
Search for other works by this author on:
Wan-Chun Li;
Wan-Chun Li
1Joslin Diabetes Center and Harvard Medical School, 1 Joslin Place, Boston, MA 02215 U.S.A.
Search for other works by this author on:
Tandy Aye;
Tandy Aye
1Joslin Diabetes Center and Harvard Medical School, 1 Joslin Place, Boston, MA 02215 U.S.A.
Search for other works by this author on:
Elena Toschi;
Elena Toschi
1Joslin Diabetes Center and Harvard Medical School, 1 Joslin Place, Boston, MA 02215 U.S.A.
Search for other works by this author on:
Arun Sharma
Arun Sharma
1Joslin Diabetes Center and Harvard Medical School, 1 Joslin Place, Boston, MA 02215 U.S.A.
Search for other works by this author on:
Biochem Soc Trans (2008) 36 (3): 353–356.
Article history
Received:
November 09 2007
Citation
Susan Bonner-Weir, Akari Inada, Shigeru Yatoh, Wan-Chun Li, Tandy Aye, Elena Toschi, Arun Sharma; Transdifferentiation of pancreatic ductal cells to endocrine β-cells. Biochem Soc Trans 1 June 2008; 36 (3): 353–356. doi: https://doi.org/10.1042/BST0360353
Download citation file:
Sign in
Don't already have an account? Register
Sign in to your personal account
You could not be signed in. Please check your email address / username and password and try again.
Could not validate captcha. Please try again.