Regulated expansion of human pancreatic β-cells

Eszter Pais, Jean Park, Tamas Alexy, Vahagn Nikolian, Shundi Ge, Kit Shaw, Shantha Senadheera, Cinnamon L. Hardee, Dianne Skelton, Roger Hollis, Gay M. Crooks, Donald B. Kohn

Research output: Contribution to journalArticlepeer-review

4 Scopus citations

Abstract

Although pancreatic Β-cell transplantation may serve as a potential cure for diabetes mellitus (DM), limited donor tissue availability poses a major challenge. Thus, there is a great demand to find new sources for pancreatic Β-cells. Here, we present a lentiviral vector-based approach to achieve Β-cell proliferation through the Β-cell-specific activation of the hepatocyte growth factor (HGF)/cmet signaling pathway. The methodology is based on the Β-cell-specific expression of a ligand-inducible, chimeric receptor (F36Vcmet), under transcriptional control of the promoter from the human insulin gene, and its ability to induce HGF/cmet signaling in the presence of a synthetic ligand (AP20187). High transduction efficiency of human pancreatic islets was achieved utilizing this approach with chimeric receptor expression confined to the Β-cell population. In addition, specific proliferation of human pancreatic Β-cells was induced utilizing this approach. Selective, regulated Β-cell expansion may help to provide greater availability of cells for transplantation in patients with DM.

Original languageEnglish (US)
Pages (from-to)1389-1396
Number of pages8
JournalMolecular Therapy
Volume18
Issue number7
DOIs
StatePublished - Jul 2010

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