title: 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.
authors.affiliation: Division of Research Immunology/Bone Marrow Transplantation, Department of Pediatrics, Childrens Hospital Los Angeles, Los Angeles, California, USA.
authors.forename: Eszter
authors.initials: E
authors.lastname: Pais
authors.forename: Jean
authors.initials: J
authors.lastname: Park
authors.forename: Tamas
authors.initials: T
authors.lastname: Alexy
authors.forename: Vahagn
authors.initials: V
authors.lastname: Nikolian
authors.forename: Shundi
authors.initials: S
authors.lastname: Ge
authors.forename: Kit
authors.initials: K
authors.lastname: Shaw
authors.forename: Shantha
authors.initials: S
authors.lastname: Senadheera
authors.forename: Cinnamon L
authors.initials: CL
authors.lastname: Hardee
authors.forename: Dianne
authors.initials: D
authors.lastname: Skelton
authors.forename: Roger
authors.initials: R
authors.lastname: Hollis
authors.forename: Gay M
authors.initials: GM
authors.lastname: Crooks
authors.forename: Donald B
authors.initials: DB
authors.lastname: Kohn
mesh_terms: D000328:Adult; D000818:Animals; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D005822:Genetic Vectors / Q000235:genetics; D019073:HT29 Cells; D017228:Hepatocyte Growth Factor / Q000235:genetics / Q000378:metabolism; D006801:Humans; D050417:Insulin-Secreting Cells / Q000166:cytology* / Q000378:metabolism; D016086:Lentivirus / Q000235:genetics; D051379:Mice; D011401:Promoter Regions, Genetic / Q000235:genetics; D046509:Tissue Culture Techniques
chemical_list: D017228:Hepatocyte Growth Factor
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