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- Title
Regulated Expansion of Human Pancreatic β-Cells.
- Authors
Pais, Eszter; Park, Jean; Alexy, Tamas; Nikolian, Vahagn; Ge, Shundi; Shaw, Kit; Senadheera, Shantha; Hardee, Cinnamon L; Skelton, Dianne; Hollis, Roger; Crooks, Gay M.; Kohn, Donald B.
- 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.
- Subjects
CELLULAR control mechanisms; PANCREATIC beta cells; DIABETES; CELL transplantation; CELL proliferation; METHODOLOGY
- Publication
Molecular Therapy, 2010, Vol 18, Issue 7, p1389
- ISSN
1525-0016
- Publication type
Article
- DOI
10.1038/mt.2010.63