title: Co-expression of fibulin-5 and VEGF165 increases long-term patency of synthetic vascular grafts seeded with autologous endothelial cells.
abstract: Small caliber synthetic vascular grafts are commonly used for bypass surgery and dialysis access sites but have high failure rates because of neointima formation and thrombosis. Seeding synthetic grafts with endothelial cells (ECs) provides a biocompatible surface that may prevent graft failure. However, EC detachment following exposure to blood flow still remains a major obstacle in the development of biosynthetic grafts. We tested the hypothesis that induced expression by the seeded EC, of vascular endothelial growth factor165 (VEGF165) and of fibulin-5, an extracellular matrix glycoprotein that has a crucial role in elastin fiber organization and increase EC adherence to surfaces, may improve long-term graft patency. Autologous ECs were isolated from venous segments, and were transduced with retroviral vectors expressing fibulin-5 and VEGF165. The modified cells were seeded on expanded polytetrafluoroethylene (ePTFE) grafts and implanted in a large animal model. Three months after transplantation, all grafts seeded with modified EC were patent on a selective angiography, whereas only a third of the control grafts were patent. Similar results were shown at 6 months. Thus, seeding ePTFE vascular grafts with genetically modified EC improved long-term small caliber graft patency. The biosynthetic grafts may provide a novel therapeutic modality for patients with peripheral vascular disease and patients requiring vascular access for hemodialysis.
authors.affiliation: Institute of Hematology, Lady Davis Carmel Medical Center, Haifa, Israel.
authors.forename: M
authors.initials: M
authors.lastname: Preis
authors.affiliation: Department of Vascular Surgery, Sheba Medical Center, Tel Hashomer and Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
authors.forename: J
authors.initials: J
authors.lastname: Schneiderman
authors.affiliation: Department of Cardiovascular Medicine, Lady Davis Carmel Medical Center, Haifa, Israel.|MultiGene Vascular Systems Ltd, Haifa, Israel.
authors.forename: B
authors.initials: B
authors.lastname: Koren
authors.affiliation: Department of Cardiovascular Medicine, Lady Davis Carmel Medical Center, Haifa, Israel.|MultiGene Vascular Systems Ltd, Haifa, Israel.
authors.forename: Y
authors.initials: Y
authors.lastname: Ben-Yosef
authors.affiliation: The Bruce Rappaport Faculty of Medicine, Technion, Israel Institute of Technology, Haifa, Israel.
authors.forename: D
authors.initials: D
authors.lastname: Levin-Ashkenazi
authors.affiliation: Immunology Research Unit, Lady Davis Carmel Medical Center, Haifa, Israel.
authors.forename: S
authors.initials: S
authors.lastname: Shapiro
authors.affiliation: Department of Cardiovascular Medicine, Lady Davis Carmel Medical Center, Haifa, Israel.|MultiGene Vascular Systems Ltd, Haifa, Israel.
authors.forename: T
authors.initials: T
authors.lastname: Cohen
authors.affiliation: Department of Cardiovascular Medicine, Lady Davis Carmel Medical Center, Haifa, Israel.
authors.forename: M
authors.initials: M
authors.lastname: Blich
authors.affiliation: Department of Cardiovascular Medicine, Lady Davis Carmel Medical Center, Haifa, Israel.|MultiGene Vascular Systems Ltd, Haifa, Israel.
authors.forename: M
authors.initials: M
authors.lastname: Israeli-Amit
authors.affiliation: Department of Cardiovascular Medicine, Lady Davis Carmel Medical Center, Haifa, Israel.|MultiGene Vascular Systems Ltd, Haifa, Israel.
authors.forename: Y
authors.initials: Y
authors.lastname: Sarnatzki
authors.affiliation: Department of Cardiovascular Medicine, Lady Davis Carmel Medical Center, Haifa, Israel.|MultiGene Vascular Systems Ltd, Haifa, Israel.
authors.forename: D
authors.initials: D
authors.lastname: Gershtein
authors.affiliation: The Bruce Rappaport Faculty of Medicine, Technion, Israel Institute of Technology, Haifa, Israel.
authors.forename: R
authors.initials: R
authors.lastname: Shofti
authors.affiliation: Department of Cardiovascular Medicine, Lady Davis Carmel Medical Center, Haifa, Israel.|MultiGene Vascular Systems Ltd, Haifa, Israel.|The Bruce Rappaport Faculty of Medicine, Technion, Israel Institute of Technology, Haifa, Israel.
authors.forename: B S
authors.initials: BS
authors.lastname: Lewis
authors.affiliation: Department of Molecular Genetics, Weizmann Institute of Science, Rehovot, Israel.
authors.forename: Y
authors.initials: Y
authors.lastname: Shaul
authors.affiliation: Department of Cardiovascular Medicine, Lady Davis Carmel Medical Center, Haifa, Israel.|MultiGene Vascular Systems Ltd, Haifa, Israel.|The Bruce Rappaport Faculty of Medicine, Technion, Israel Institute of Technology, Haifa, Israel.
authors.forename: M Y
authors.initials: MY
authors.lastname: Flugelman
mesh_terms: D000818:Animals; D042783:Endothelial Cells / Q000502:physiology / Q000637:transplantation*; D016326:Extracellular Matrix Proteins / Q000235:genetics / Q000627:therapeutic use*; D006801:Humans; D023421:Models, Animal; D016491:Peripheral Vascular Diseases / Q000628:therapy*; D051381:Rats; D012756:Sheep; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000627:therapeutic use*; D058017:Vascular Grafting / Q000379:methods*; D014654:Vascular Patency
chemical_list: D016326:Extracellular Matrix Proteins; C492373:FBLN5 protein, human; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A