Coexpression of vascular endothelial growth factor and interleukin-1 receptor antagonist for improved human islet survival and function

Xiangxu Jia, Kun Cheng, Ram I. Mahato

Research output: Contribution to journalArticle

19 Scopus citations

Abstract

Ex vivo gene therapy approaches can improve the outcome of islet transplantation for treating type I diabetes. We have recently shown improvement in islet survival and function following ex vivo infection of islets with a mixture of adenoviral vectors encoding human vascular endothelial growth factor (Adv-hVEGF) and human interleukin-1 receptor antagonist (Adv-hIL-1Ra). In this study, we constructed a bicistronic vector encoding these two genes (phVEGF-hIL-1Ra) by cloning hIL-1Ra under the cytomegalovirus (CMV) promoter and hVEGF under the elongation factor-1α (EF-1 α) promoter in pBudCE4.1 vector. There was dose and time dependent expression of hVEGF and hIL-1Ra at both mRNA and protein levels after transfection with human islets. Transfected islets were viable, as evidenced by insulin release upon glucose challenge. Coexpression of hVEGF and hIL-1Ra suppressed nitric oxide production, total caspases, apoptosis, and necrosis in the presence of inflammatory cytokine cocktail consisting of IL-1β, TNFα, and IFNγ. In conclusion, our results indicated that coexpression of growth factor and antiapoptic genes can improve islet survival and function.

Original languageEnglish (US)
Pages (from-to)199-207
Number of pages9
JournalMolecular Pharmaceutics
Volume4
Issue number2
DOIs
StatePublished - Mar 2007

Keywords

  • Bicistronic plasmid
  • Human islet
  • Insulin release
  • Real-time RT-PCR
  • hIL-1Ra
  • hVEGF

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmaceutical Science
  • Drug Discovery

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