Adenoviral infection or deferoxamine? Two approaches to overexpress VEGF in beta-cell lines.
Rapid and adequate revascularization of transplanted islets is important for their survival and function during transplantation. Vascular endothelial growth factor (VEGF) could play a critical role with respect to islet revascularization. The aim of this study was to compare two strategies that are used to overexpress VEGF in beta-cells: (1) gene therapy through adenoviral infection and (2) a pharmacological approach using deferoxamine (DFO). beta-Cell lines from rat insulinoma (RINm5F) were either infected using an adenovirus encoding the gene of human VEGF 165 or incubated with DFO. One day after treatment, the viability of RINm5F cells was preserved with 10 micromol/L of DFO (103.95 +/- 5.66% toward control; n = 4). In addition, adenoviral infection maintained the viability of cells for all the concentrations used. In both treatments, overexpression of VEGF was in a comparable level. Finally, the ratio of Bax/Bcl-2 indicated that the apoptosis increased in infected beta-cells whereas treatment with DFO seems to be antiapoptotic. Our results suggest that the use of DFO could be a realistic approach to improve the vascularization of islets during transplantation.
Langlois
Allan
A
Centre européen d'étude du Diabète, Boulevard René Leriche, BP 30029, 67033 Strasbourg Cedex 2, France. a.langlois@ceed-diabete.org
Bietiger
William
W
Sencier
Marie-Christine
MC
Maillard
Elisa
E
Pinget
Michel
M
Kessler
Laurence
L
Sigrist
Severine
S
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects / Q000235:genetics; D003676:Deferoxamine / Q000494:pharmacology*; D005786:Gene Expression Regulation; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors; D006801:Humans; D007340:Insulinoma / Q000235:genetics / Q000378:metabolism; D016381:Islets of Langerhans Transplantation / Q000379:methods*; D018919:Neovascularization, Physiologic / Q000235:genetics; D010190:Pancreatic Neoplasms / Q000235:genetics / Q000378:metabolism; D051381:Rats; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics*
D042461:Vascular Endothelial Growth Factor A; D003676:Deferoxamine