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Mol Ther. 2010 Jul;18(7):1389-96. doi: 10.1038/mt.2010.63. Epub 2010 Apr 13.

Regulated expansion of human pancreatic beta-cells.

Author information

1
Division of Research Immunology/Bone Marrow Transplantation, Department of Pediatrics, Childrens Hospital Los Angeles, Los Angeles, California, USA.

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.

PMID:
20389286
PMCID:
PMC2911252
DOI:
10.1038/mt.2010.63
[Indexed for MEDLINE]
Free PMC Article

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