Regulated expansion of human pancreatic beta-cells.
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.
Pais
Eszter
E
Division of Research Immunology/Bone Marrow Transplantation, Department of Pediatrics, Childrens Hospital Los Angeles, Los Angeles, California, USA.
Park
Jean
J
Alexy
Tamas
T
Nikolian
Vahagn
V
Ge
Shundi
S
Shaw
Kit
K
Senadheera
Shantha
S
Hardee
Cinnamon L
CL
Skelton
Dianne
D
Hollis
Roger
R
Crooks
Gay M
GM
Kohn
Donald B
DB
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
D017228:Hepatocyte Growth Factor
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