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.
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On the length, weight and GC content of the human genome
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- Authors
- Preis, M., Schneiderman, J., Koren, B., Ben-Yosef, Y., Levin-Ashkenazi, D., Shapiro, S., Cohen, T., Blich, M., Israeli-Amit, M., Sarnatzki, Y., Gershtein, D., Shofti, R., Lewis, B. S., Shaul, Y., & Flugelman, M. Y.
- Affiliations
- Carmel Medical Center (IL)
- Tel Aviv University (IL)
- Technion – Israel Institute of Technology (IL)
- Weizmann Institute of Science (IL)
- Corresponding author
- Flugelman, M Y
- Venue
- Gene Therapy
- Published
- 2015-12-24
- Volume
- 23
- Issue
- 3
- Pages
- 237-246
- ISSN
- 0969-7128 (ISSN-L)
- 1476-5462
- OpenAlex
- W2174352515
- Cited by
- 13
- References
- 48
- Citations by year
- 2025: 3 · 2023: 1 · 2021: 3 · 2019: 3 · 2018: 1 · 2017: 2
- FWCI
- 1.01
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Gene Therapy (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Surgery › Tissue Engineering and Regenerative Medicine
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Angiogenesis and VEGF in Cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Virus-based gene therapy research
- Keywords
- fibulin-5, VEGF165, endothelial cell seeding, synthetic vascular grafts, expanded polytetrafluoroethylene, graft patency, neointima formation, thrombosis, endothelial cell detachment, retroviral gene transfer, hemodialysis vascular access, peripheral vascular disease
- MeSH terms
- Animals, Humans, Sheep, Vascular Patency, Extracellular Matrix Proteins, Peripheral Vascular Diseases, Models, Animal, Vascular Endothelial Growth Factor A, Endothelial Cells, Rats, Vascular Grafting
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