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Tissue-Specific Stem Cells
Article first published online: 22 JUL 2010
Copyright © 2010 AlphaMed Press
Volume 28, Issue 9, pages 1630–1638, September 2010
How to Cite
Chung, C.-H., Hao, E., Piran, R., Keinan, E. and Levine, F. (2010), Pancreatic β-Cell Neogenesis by Direct Conversion from Mature α-Cells. STEM CELLS, 28: 1630–1638. doi: 10.1002/stem.482
Author contributions: C.-H.C.: conception and design, collection and/or assembly of data, data analysis and interpretation, manuscript writing; E.H.: collection and/or assembly of data; R.P.: collection and/or assembly of data; E.K.: useful discussions; F.L.: conception and design, manuscript writing, final approval of manuscript.
Disclosure of potential conflicts of interest is found at the end of this article.
First published online in STEM CELLS EXPRESS July 22, 2010.
- Issue published online: 22 JUL 2010
- Article first published online: 22 JUL 2010
- Manuscript Accepted: 7 JUL 2010
- Manuscript Received: 26 MAY 2010
- Sanford Children's Health Research Center
- Juvenile Diabetes Research Foundation
- Mackay Memorial Hospital
- National Science Foundation, Skaggs Institute for Chemical Biology at the Scripps Research Institute
- Stem cell;
Because type 1 and type 2 diabetes are characterized by loss of β-cells, β-cell regeneration has garnered great interest as an approach to diabetes therapy. Here, we developed a new model of β-cell regeneration, combining pancreatic duct ligation (PDL) with elimination of pre-existing β-cells with alloxan. In this model, in which virtually all β-cells observed are neogenic, large numbers of β-cells were generated within 2 weeks. Strikingly, the neogenic β-cells arose primarily from α-cells. α-cell proliferation was prominent following PDL plus alloxan, providing a large pool of precursors, but we found that β-cells could form from α-cells by direct conversion with or without intervening cell division. Thus, classical asymmetric division was not a required feature of the process of α- to β-cell conversion. Intermediate cells coexpressing α-cell- and β-cell-specific markers appeared within the first week following PDL plus alloxan, declining gradually in number by 2 weeks as β-cells with a mature phenotype, as defined by lack of glucagon and expression of MafA, became predominant. In summary, these data revealed a novel function of α-cells as β-cell progenitors. The high efficiency and rapidity of this process make it attractive for performing the studies required to gain the mechanistic understanding of the process of α- to β-cell conversion that will be required for eventual clinical translation as a therapy for diabetes. STEM CELLS 2010; 28:1630–1638.