48 0

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

Title
Effect of hypoxia-inducible VEGF gene expression on revascularization and graft function in mouse islet transplantation
Author
이민형
Keywords
hypoxia; islet; RTP801; transplantation; vascular endothelial growth factor
Issue Date
2011-03
Publisher
WILEY, 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
Citation
TRANSPLANT INTERNATIONAL,권: 24 호: 3 페이지: 307-314
Abstract
P>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.
URI
http://onlinelibrary.wiley.com/doi/10.1111/j.1432-2277.2010.01194.x/http://hdl.handle.net/20.500.11754/66438
ISSN
0934-0874; 1432-2277
DOI
10.1111/j.1432-2277.2010.01194.x
Appears in Collections:
COLLEGE OF ENGINEERING[S](공과대학) > BIOENGINEERING(생명공학과) > Articles
Files in This Item:
There are no files associated with this item.
Export
RIS (EndNote)
XLS (Excel)
XML


qrcode

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.

BROWSE