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Effect of hypoxia-inducible VEGF gene expression on revascularization and graft function in mouse islet transplantation.

 Byung Wan Lee  ;  Minhyung Lee  ;  Hee Young Chae  ;  Sanghyun Lee  ;  Jun Goo Kang  ;  Chul Sik Kim  ;  Seong Jin Lee  ;  Hyung Joon Yoo  ;  Sung-Hee Ihm 
 TRANSPLANT INTERNATIONAL, Vol.24(3) : 307-314, 2011 
Journal Title
Issue Date
Animals ; Diabetes Mellitus, Experimental/metabolism ; Genetic Therapy/methods ; Graft Survival ; Humans ; Hypoxia/metabolism ; Islets of Langerhans/blood supply* ; Islets of Langerhans/physiology ; Islets of Langerhans Transplantation/methods ; Islets of Langerhans Transplantation/physiology* ; Male ; Mice ; Neovascularization, Physiologic/drug effects* ; Transfection ; Vascular Endothelial Growth Factor A/biosynthesis ; Vascular Endothelial Growth Factor A/physiology ; Vascular Endothelial Growth Factor A/therapeutic use*
hypoxia ; islet ; RTP801 ; transplantation ; vascular endothelial growth factor
For gene transfer strategies to improve islet engraftment, vascular endothelial growth factor (VEGF) expression should be regulated in a way that matches the transient nature of revascularization with simultaneously avoiding undesirable effects of overexpression. The aim of this study was to investigate the effects of hypoxia-inducible VEGF gene transfer using the RTP801 promoter on islet grafts. We implanted pSV-hVEGF transfected, pRTP801-hVEGF transfected or nontransfected mouse islets under the kidney capsule of streptozotocin-induced diabetic syngeneic mice. Human VEGF immunostaining of day 3 grafts revealed that the pRTP801-hVEGF transfected group had higher hVEGF expression compared with the pSV-hVEGF transfected group. BS-1 staining of day 3 grafts from the pRTP801-hVEGF transfected group showed the highest vascular density, which was comparable with day 6 grafts from the nontransfected group. In 360 islet equivalent (IEQ)-transplantation which reverted hyperglycemia in all mice, the area under the curve of glucose levels during intraperitoneal glucose tolerance test 7 weeks post-transplant was lower in mice transplanted with pRTP801-hVEGF transfected grafts compared with mice transplanted with nontransfected grafts. In 220 IEQ-transplantations, diabetic mice transplanted with pRTP801-hVEGF islets became normoglycemic more rapidly compared with mice transplanted with pSV-hVEGF or nontransfected islets, and diabetes reversal rate after 50 days was 90%, 68%, and 50%, respectively. In conclusion, our results indicate that regulated overexpression of hVEGF in a hypoxia-inducible manner enhances islet vascular engraftment and preserves islet function overtime in transplants
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1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
Yonsei Authors
Lee, Byung Wan(이병완) ORCID logo https://orcid.org/0000-0002-9899-4992
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