Adenovirus-based vascular endothelial growth factor gene delivery to human pancreatic islets

Gene Therapy
K ChengRam I Mahato

Abstract

Islet transplantation is limited by islet graft failure due to poor revascularization, host immune rejection and nonspecific inflammatory response. Delivery of human vascular endothelial growth factor (hVEGF) gene to the islets is likely to promote islet revascularization and survival. We used a bicistronic adenoviral vector encoding hVEGF and CpG-free allele of green fluorescent protein (Adv-GFP-hVEGF) and introduced into human pancreatic islets by transfection. We found that transfection efficiency and apoptosis were dependent on the multiplicity of infection (MOI). Compared to Adv-GFP transfected and nontransfected islets, the levels of hVEGF secreted from Adv-GFP-hVEGF transfected islets were higher and exhibit a linear relationship between hVEGF expression and MOI (10-5000). Persistent, but low level expression of hVEGF from nontransfected islets was also observed. This may be due to expression of the endogenous hVEGF gene under hypoxic conditions. The levels of DNA fragmentation determined by ELISA of islet lysates were dependent on the MOI of Adv-GFP-hVEGF. On glucose challenge, insulin release from transfected islets was comparable to nontransfected islets. Immunohistochemical staining for hVEGF was very high in Adv-GFP...Continue Reading

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Citations

Nov 13, 2008·Pharmaceutical Research·Ravikiran Panakanti, Ram I Mahato
May 20, 2011·Molecular Pharmaceutics·Husnain Kh HaiderMuhammad Ashraf
Jun 29, 2011·Molecular Pharmaceutics·Hao WuRam I Mahato
Dec 11, 2008·Molecular Pharmaceutics·Ravikiran Panakanti, Ram I Mahato
Jul 8, 2009·Diabetes Technology & Therapeutics·Han Chang Kang, You Han Bae
Sep 25, 2010·Breast Cancer Research : BCR·Bin Qin, Kun Cheng
Jul 25, 2013·Annals of Biomedical Engineering·Andrés J García
Jun 2, 2007·Journal of Drug Targeting·Daniel De PaulaRam I Mahato
Jun 17, 2009·Journal of Drug Targeting·Allan LangloisSeverine Sigrist
Dec 25, 2008·Journal of Drug Targeting·Hyun Ah KimMinhyung Lee
Dec 16, 2010·Advanced Drug Delivery Reviews·Feng Li, Ram I Mahato
Apr 21, 2009·Journal of Controlled Release : Official Journal of the Controlled Release Society·Ram I Mahato
Sep 20, 2006·American Journal of Transplantation : Official Journal of the American Society of Transplantation and the American Society of Transplant Surgeons·V CantaluppiG Camussi
Apr 26, 2006·Clinical and Experimental Immunology·T LinnD Brandhorst
Jan 26, 2013·Transplant International : Official Journal of the European Society for Organ Transplantation·Hee Young ChaeSung-Hee Ihm
Dec 17, 2011·Transplant International : Official Journal of the European Society for Organ Transplantation·Hee Young ChaeSung-Hee Ihm
Dec 9, 2010·Transplant International : Official Journal of the European Society for Organ Transplantation·Byung Wan LeeSung-Hee Ihm
Mar 6, 2012·Diabetes/metabolism Research and Reviews·Daniel LazardKonstantin Bloch
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Mar 20, 2015·Drug Delivery and Translational Research·Edward A PhelpsAndrés J García
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Feb 3, 2018·Islets·Anissa GambleA M James Shapiro
May 23, 2006·Pharmacological Reviews·Ajit S Narang, Ram I Mahato
May 10, 2018·Frontiers in Endocrinology·Jessie M Barra, Hubert M Tse

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