Induction of angiogenesis in omentum with vascular endothelial growth factor: influence on the viability of encapsulated rat pancreatic islets during transplantation.
Transplantation of pancreatic islets is proposed as a treatment for type 1 diabetes, but insufficient blood supply can cause the loss of viable grafted islets. In the present study, we investigated the influence of vascular endothelial growth factor (VEGF) on the angiogenesis of omentum during encapsulated islet allotransplantation and consequently on islet survival. Fifty rat islets, cultured for 24 h, were encapsulated in the presence or absence of human VEGF and implanted in the peritoneal cavity of rats (n = 6). After 7, 14 and 28 days of implantation, encapsulation devices with surrounding omentum were removed. Histological analysis of this tissue was performed. Cellular adhesion at the membrane surface was characterized by a phagocytosis test. The morphological aspect of the islets was analyzed and their functionality was evaluated by measuring insulin secretion. At each step of the study, there was a two-fold increase in the number of vessels in the presence of VEGF. In addition, VEGF increased the vessel diameter and the surface area of the angiogenic pedicle. Moreover, the presence of VEGF significantly decreased the distance between the devices and vessels (16.2 +/- 5.6 vs. 51.6 +/- 10.1 microm, p < 0.001). Membrane surface analysis showed a decrease in macrophage adhesion in the presence of VEGF. Furthermore, islet structure and functionality was preserved in the presence of VEGF. Stimulation of angiogenesis of omentum induced by VEGF is associated with preservation of islet viability. Local delivery of VEGF proved to be a relevant approach to ameliorate the outcome of islet transplantation.
Sigrist
S
S
Centre européen d'étude du Diabète, Faculté de Médecine, Hôpital de Hautepierre, Strasbourg, France.
Mechine-Neuville
A
A
Mandes
K
K
Calenda
V
V
Legeay
G
G
Bellocq
J-P
JP
Pinget
M
M
Kessler
L
L
D000818:Animals; D002470:Cell Survival / Q000502:physiology; D002478:Cells, Cultured; D018914:Cells, Immobilized / Q000166:cytology / Q000637:transplantation; D003922:Diabetes Mellitus, Type 1 / Q000601:surgery; D004339:Drug Compounding; D016228:Endothelial Growth Factors / Q000494:pharmacology*; D006085:Graft Survival; D036341:Intercellular Signaling Peptides and Proteins / Q000494:pharmacology*; D007515:Islets of Langerhans / Q000098:blood supply* / Q000166:cytology; D016381:Islets of Langerhans Transplantation / Q000379:methods*; D008222:Lymphokines / Q000494:pharmacology*; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D009852:Omentum / Q000098:blood supply*; D051381:Rats; D017208:Rats, Wistar; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D016228:Endothelial Growth Factors; D036341:Intercellular Signaling Peptides and Proteins; D008222:Lymphokines; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors