Effective glycemic control achieved by transplanting non-viral cationic liposome-mediated VEGF-transfected islets in streptozotocin-induced diabetic mice.
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 microg/microgL cDNA and 25 microgL 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.
Chae
Hee Young
HY
Samsung Biomedical Research Institute, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 100-380, Korea.
Lee
Byung Wan
BW
Oh
Seung Hoon
SH
Ahn
You Ran
YR
Chung
Jae Hoon
JH
Min
Yong Ki
YK
Lee
Myung Shik
MS
Lee
Moon Kyu
MK
Kim
Kwang Won
KW
D000818:Animals; D001835:Body Weight; D002470:Cell Survival; D003921:Diabetes Mellitus, Experimental / Q000150:complications* / Q000378:metabolism; D004195:Disease Models, Animal; D005947:Glucose / Q000494:pharmacology; D005951:Glucose Tolerance Test; D006943:Hyperglycemia / Q000150:complications / Q000378:metabolism* / Q000628:therapy*; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000098:blood supply / Q000166:cytology / Q000378:metabolism; D016381:Islets of Langerhans Transplantation; D008081:Liposomes / Q000008:administration & dosage* / Q000737:chemistry; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D018919:Neovascularization, Physiologic; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013311:Streptozocin; D014162:Transfection; D042442:Vascular Endothelial Growth Factors / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism*
D007328:Insulin; D008081:Liposomes; D012333:RNA, Messenger; D042442:Vascular Endothelial Growth Factors; D013311:Streptozocin; D005947:Glucose