Effective glycemic control achieved by transplanting non-viral cationic liposome-mediated VEGF-transfected islets in streptozotocin-induced diabetic mice.
- Author:
Hee Young CHAE
1
;
Byung Wan LEE
;
Seung Hoon OH
;
You Ran AHN
;
Jae Hoon CHUNG
;
Yong Ki MIN
;
Myung Shik LEE
;
Moon Kyu LEE
;
Kwang Won KIM
Author Information
1. Samsung Biomedical Research Institute, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 100-380, Korea.
- Publication Type:Original Article ; Research Support, Non-U.S. Gov't
- Keywords:
cationic lipid reagent;
diabetes mellitus;
gene therapy;
gene transfer techniques;
islet of Langerhans transplantation;
vascular endothelial growth factor
- MeSH:
Animals;
Body Weight;
Cell Survival;
Diabetes Mellitus, Experimental/*complications/metabolism;
Disease Models, Animal;
Glucose/pharmacology;
Glucose Tolerance Test;
Hyperglycemia/complications/*metabolism/*therapy;
Insulin/secretion;
Islets of Langerhans/blood supply/cytology/secretion;
*Islets of Langerhans Transplantation;
Liposomes/*administration & dosage/chemistry;
Male;
Mice;
Mice, Inbred BALB C;
Neovascularization, Physiologic;
RNA, Messenger/genetics/metabolism;
Research Support, Non-U.S. Gov't;
Streptozocin;
Transfection;
Vascular Endothelial Growth Factors/biosynthesis/*genetics/*metabolism/secretion
- From:Experimental & Molecular Medicine
2005;37(6):513-523
- CountryRepublic of Korea
- Language:English
-
Abstract:
Hypoxic damage is one of the major causes of islet graft failure and VEGF is known to play a crucial role in revascularization. To address the effectiveness of a cationic lipid reagent as a VEGF gene carrier, and the beneficial effect of VEGF-transfected islets on glycemic control, we used effectene lipid reagent in a transfection experiment using mouse islets. Transfection efficiencies were highest for 4 microgram/microliter cDNA and 25 microliter effectene and cell viabilities were also satisfactory under this condition, and the overproduction of VEGF mRNA and protein were confirmed from conditioned cells. A minimal number of VEGF-transfected islets (100 IEQ/animal) were transplanted into streptozotocin (STZ)-induced diabetic mice. Hyperglycemia was not controlled in the islet transplantation (IT)-alone group (0/8) (non- diabetic glucose mice number/total recipient mice number) or in the IT-pJDK control vector group (0/8). However, hyperglycemia was completely abrogated in the IT-pJDK-VEGF transduced group (8/8), and viable islets and increased VEGF-transfected grafts vascularization were observed in renal capsules.
