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Regulated expansion of human pancreatic beta-cells.

Abstract
Although pancreatic beta-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 beta-cells. Here, we present a lentiviral vector-based approach to achieve beta-cell proliferation through the beta-cell-specific activation of the hepatocyte growth factor (HGF)/cmet signaling pathway. The methodology is based on the beta-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 beta-cell population. In addition, specific proliferation of human pancreatic beta-cells was induced utilizing this approach. Selective, regulated beta-cell expansion may help to provide greater availability of cells for transplantation in patients with DM.
AuthorsEszter 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
JournalMolecular therapy : the journal of the American Society of Gene Therapy (Mol Ther) Vol. 18 Issue 7 Pg. 1389-96 (Jul 2010) ISSN: 1525-0024 [Electronic] United States
PMID20389286 (Publication Type: Journal Article)
Chemical References
  • Hepatocyte Growth Factor
Topics
  • Adult
  • Animals
  • Cell Line, Tumor
  • Cell Proliferation
  • Genetic Vectors (genetics)
  • HT29 Cells
  • Hepatocyte Growth Factor (genetics, metabolism)
  • Humans
  • Insulin-Secreting Cells (cytology, metabolism)
  • Lentivirus (genetics)
  • Mice
  • Promoter Regions, Genetic (genetics)
  • Tissue Culture Techniques

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