Study for the Improvement of Early Implantation and Long Term Graft Survival in Pancreatic Islet Cell Transplantation by Induction of Angiogenesis with Gene Transfection of Vascuar Endothelial Growth Factor / 대한이식학회지

ABSTRACT

PURPOSE: Transplantation of pancreas islet has been worldwidely studied as a one of therapeutic modalities to achieve the insulin independence. We studied whether the expression of vascular endothelial growth factor (VEGF) on pancreas islets with liposomal VEGF gene transfer could improve the efficacy of early implantation and long term graft survival in pancreatic islet cell transplantation. METHODS: Syngenic pancreas islets were transplanted beneath the renal capsule. Islets were transfected with plasmid VEGF c-DNA using cationic liposome DMRIE-C. Glucose metabolism and histologic findings were compared between the groups transplanted with VEGF DNA containing islets (n=5) and the control group with (n=5) or without (n=4) local recombinant VEGF adminstration during islet transplant. RESULTS: Glucose was controlled at 5.5 days after transplantation in control group without r-VEGF adminstration, at 4 days in group with recombinant VEGF adminstration, and at 6.6 days in group with VEGF DNA transfected islets. Euglycemia was maintained over 150 days in control group. However, graft failure was developed in 22 days after transplantation in group with VEGF DNA transfected islet. Histologically there were severe infiltrations of neutrophil and lymphocyte in VEGF DNA transfected grafts from 5 days after transplantation. CONCLUSION: Although VEGF could be a favorable angiogenic factor in pancreas islet transplantation, VEGF expression following VEGF DNA transfection into islets could not increase the graft survival due to inflammatory process. More investigations are needed to clarify the mechanism on destructive process of islets after gene transfection into islets, and another approaches to get the effect of gene transfection should be followed.