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.
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Authors | 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 |
Journal | Molecular 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 |
PMID | 20389286
(Publication Type: Journal Article)
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Chemical References |
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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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