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.
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