Exp Mol Med.  2005 Dec;37(6):513-523.

Effective glycemic control achieved by transplanting non-viral cationic liposome-mediated VEGF-transfected islets in streptozotocin-induced diabetic mice

• Chae HY
• Lee BW
• Oh SH
• Ahn YR
• Chung JH
• Min YK
• Lee MS
• Lee MK
• Kim KW

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.

Keyword

cationic lipid reagent; diabetes mellitus; gene therapy; gene transfer techniques; islet of Langerhans transplantation; vascular endothelial growth factor

MeSH Terms

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