Work

Coexpression of Vascular Endothelial Growth Factor and Interleukin-1 Receptor Antagonist for Improved Human Islet Survival and Function

Year: 2007

Type: article

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-1alpha (EF-1 alpha) 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-1beta, TNFalpha, and IFNgamma. In conclusion, our results indicated that coexpression of growth factor and antiapoptic genes can improve islet survival and function.

Source: Molecular Pharmaceutics

DOI: 10.1021/mp060091s

Authors: Xiangxu Jia, Kun Cheng, Ram I. Mahato

Institution: University of Tennessee Health Science Center

Language: English

Topic: Pancreatic function and diabetes

Subfield: Surgery

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: green

Funder: National Institute of Diabetes and Digestive and Kidney Diseases