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

byungwan lee, Minhyung Lee, Hee Young Chae, Sanghyun Lee, Jun Goo Kang, Chul Sik Kim, Seong Jin Lee, Hyung Joon Yoo, Sung Hee Ihm

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

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. Transplant International

Original languageEnglish
Pages (from-to)307-314
Number of pages8
JournalTransplant International
Volume24
Issue number3
DOIs
Publication statusPublished - 2011 Mar 1

Fingerprint

Islets of Langerhans Transplantation
Vascular Endothelial Growth Factor A
Transplants
Gene Expression
Blood Vessels
Hypoxia
Glucose Tolerance Test
Streptozocin
Hyperglycemia
Genes
Area Under Curve
Capsules
Staining and Labeling
Kidney
Glucose

All Science Journal Classification (ASJC) codes

  • Transplantation

Cite this

lee, byungwan ; Lee, Minhyung ; Chae, Hee Young ; Lee, Sanghyun ; Kang, Jun Goo ; Kim, Chul Sik ; Lee, Seong Jin ; Yoo, Hyung Joon ; Ihm, Sung Hee. / Effect of hypoxia-inducible VEGF gene expression on revascularization and graft function in mouse islet transplantation. In: Transplant International. 2011 ; Vol. 24, No. 3. pp. 307-314.
@article{0e870510d2f04bfcbf4b2dce2c439efe,
title = "Effect of hypoxia-inducible VEGF gene expression on revascularization and graft function in mouse islet transplantation",
abstract = "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. Transplant International",
author = "byungwan lee and Minhyung Lee and Chae, {Hee Young} and Sanghyun Lee and Kang, {Jun Goo} and Kim, {Chul Sik} and Lee, {Seong Jin} and Yoo, {Hyung Joon} and Ihm, {Sung Hee}",
year = "2011",
month = "3",
day = "1",
doi = "10.1111/j.1432-2277.2010.01194.x",
language = "English",
volume = "24",
pages = "307--314",
journal = "Transplant International",
issn = "0934-0874",
publisher = "Wiley-Blackwell",
number = "3",

}

Effect of hypoxia-inducible VEGF gene expression on revascularization and graft function in mouse islet transplantation. / lee, byungwan; Lee, Minhyung; Chae, Hee Young; Lee, Sanghyun; Kang, Jun Goo; Kim, Chul Sik; Lee, Seong Jin; Yoo, Hyung Joon; Ihm, Sung Hee.

In: Transplant International, Vol. 24, No. 3, 01.03.2011, p. 307-314.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Effect of hypoxia-inducible VEGF gene expression on revascularization and graft function in mouse islet transplantation

AU - lee, byungwan

AU - Lee, Minhyung

AU - Chae, Hee Young

AU - Lee, Sanghyun

AU - Kang, Jun Goo

AU - Kim, Chul Sik

AU - Lee, Seong Jin

AU - Yoo, Hyung Joon

AU - Ihm, Sung Hee

PY - 2011/3/1

Y1 - 2011/3/1

N2 - 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. Transplant International

AB - 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. Transplant International

UR - http://www.scopus.com/inward/record.url?scp=79551542032&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=79551542032&partnerID=8YFLogxK

U2 - 10.1111/j.1432-2277.2010.01194.x

DO - 10.1111/j.1432-2277.2010.01194.x

M3 - Article

C2 - 21138485

AN - SCOPUS:79551542032

VL - 24

SP - 307

EP - 314

JO - Transplant International

JF - Transplant International

SN - 0934-0874

IS - 3

ER -