Document Detail


Regulated expansion of human pancreatic beta-cells.
MedLine Citation:
PMID:  20389286     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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:
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
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Publication Detail:
Type:  In Vitro; Journal Article     Date:  2010-04-13
Journal Detail:
Title:  Molecular therapy : the journal of the American Society of Gene Therapy     Volume:  18     ISSN:  1525-0024     ISO Abbreviation:  Mol. Ther.     Publication Date:  2010 Jul 
Date Detail:
Created Date:  2010-07-02     Completed Date:  2010-09-30     Revised Date:  2013-05-29    
Medline Journal Info:
Nlm Unique ID:  100890581     Medline TA:  Mol Ther     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1389-96     Citation Subset:  IM    
Affiliation:
Division of Research Immunology/Bone Marrow Transplantation, Department of Pediatrics, Childrens Hospital Los Angeles, Los Angeles, California, USA.
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MeSH Terms
Descriptor/Qualifier:
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
Chemical
Reg. No./Substance:
67256-21-7/Hepatocyte Growth Factor
Comments/Corrections

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