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

Exp Mol Med. 2005 Dec 31;37(6):513-23. doi: 10.1038/emm.2005.64.

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 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Body Weight
  • Cell Survival
  • Diabetes Mellitus, Experimental / complications*
  • Diabetes Mellitus, Experimental / metabolism
  • Disease Models, Animal
  • Glucose / pharmacology
  • Glucose Tolerance Test
  • Hyperglycemia / complications
  • Hyperglycemia / metabolism*
  • Hyperglycemia / therapy*
  • Insulin / metabolism
  • Insulin Secretion
  • Islets of Langerhans / blood supply
  • Islets of Langerhans / cytology
  • Islets of Langerhans / metabolism
  • Islets of Langerhans Transplantation*
  • Liposomes / administration & dosage*
  • Liposomes / chemistry
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Neovascularization, Physiologic
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Streptozocin
  • Transfection
  • Vascular Endothelial Growth Factors / biosynthesis
  • Vascular Endothelial Growth Factors / genetics*
  • Vascular Endothelial Growth Factors / metabolism*

Substances

  • Insulin
  • Liposomes
  • RNA, Messenger
  • Vascular Endothelial Growth Factors
  • Streptozocin
  • Glucose