Details

Autor(en) / Beteiligte

• Chung, Cheng‐Ho
• Hao, Ergeng
• Piran, Ron
• Keinan, Ehud
• Levine, Fred

Titel

Pancreatic β‐Cell Neogenesis by Direct Conversion from Mature α‐Cells

Ist Teil von

• Stem cells (Dayton, Ohio), 2010-09, Vol.28 (9), p.1630-1638

Ort / Verlag

Hoboken: Wiley Subscription Services, Inc., A Wiley Company

Erscheinungsjahr

2010

Quelle

MEDLINE

Beschreibungen/Notizen

• 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.