Engineering blood vessels by gene and cell therapy

Zarbiv, Gabriel; Preis, Meir; Ben-Yosef, Yaara; Flugelman, Moshe Y.

doi:10.1517/14712598.7.8.1183

Cited by 7 publications

(2 citation statements)

References 97 publications

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“…The challenge of making a conduit for a hemodialysis access site is enormous, from biological and clinical perspectives. 12,13 The response of the vasculature to the surgical trauma and the change in shear stress after the creation of an access site lead to scar formation that is more pronounced on the venous side. Scar formation is dominated by inflammation and SMCs that dedifferentiate and produce an extracellular matrix that protrudes into the vascular lumen, reduces blood flow, and eventually leads to access site thrombosis and occlusion.…”

Section: Discussionmentioning

confidence: 99%

Improved Patency of ePTFE Grafts as a Hemodialysis Access Site by Seeding Autologous Endothelial Cells Expressing Fibulin-5 and VEGF

et al. 2018

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Small caliber synthetic vascular grafts used for dialysis access sites have high failure rates due to neointima formation and thrombosis. Seeding synthetic grafts with endothelial cells (ECs) provides a biocompatible surface that may prevent graft failure. We tested the use of ePTFE grafts seeded with autologous ECs expressing fibulin-5 and vascular endothelial growth factor (VEGF), as a dialysis access site in a porcine model. We connected the carotid arteries and jugular veins of 12 miniature pigs using 7-mm ePTFE grafts; five grafts were seeded with autologous venous ECs modified to express fibulin-5 and VEGF, and seven unseeded grafts were implanted at the same location and served as controls. At 6 months, after completion of angiography, the carotid arteries and jugular veins with the connecting grafts were excised and fixed. Autologous EC isolation and transduction and graft seeding were successful in all animals. At 3 months, 4 of 5 seeded grafts and 3 of 7 control grafts were patent. At 6 months, 4 of 5 (80%) seeded grafts and only 2 of 7 (29%) control grafts were patent. Seeding ePTFE vascular grafts with genetically modified ECs improved long term small caliber graft patency. The biosynthetic grafts offer a novel therapeutic modality for vascular access in hemodialysis.

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Section: Discussionmentioning

confidence: 99%

Improved Patency of ePTFE Grafts as a Hemodialysis Access Site by Seeding Autologous Endothelial Cells Expressing Fibulin-5 and VEGF

et al. 2018

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“…36 Endothelial cells seeded within tissue engineered vascular grafts have been modified to reduce the rate of thrombogenesis and neointimal hyperplasia. 15 They have also been modified to increase their production of extracellular matrix in order to provide an adhesive material coating.…”

Section: Genetic Modulation In Vascular Tissue Engineeringmentioning

confidence: 99%

Enhancement of Endothelial Cell Retention on ePTFE Vascular Constructs by siRNA-Mediated SHP-1 or SHP-2 Gene Silencing

Tefft¹,

Kopacz²,

Liu

et al. 2015

Cel. Mol. Bioeng.

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Insufficient retention of endothelial cells to the luminal surface of small-diameter tissue engineered vascular grafts has precluded clinical translation. This study utilized a gene silencing strategy to enhance the adhesion strength of vascular endothelial cells to fibronectin-coated expanded polytetrafluoroethylene, a common vascular graft material. SHP-1 and SHP-2 are both phosphatases known to inhibit the formation of focal contacts. By employing siRNA to knockdown the expression of SHP-1 or SHP-2, we observed a significant improvement in cell retention following 6 h of pulsatile fluid shear stress. At an average fluid shear stress of 15 dyn/cm 2 , cell retention was improved from approximately 30% for control groups to approximately 70 and 85% for cells treated with SHP-1 and SHP-2 specific siRNA, respectively (n = 8 for all groups). We also observed that treatment with SHP-1 or SHP-2 specific siRNA caused a modest increase in focal contact density and did not cause a significant effect on the expression of the endothelial cell markers VEGFR-2, VE-cadherin, and PECAM-1. These findings indicate that molecular modulation may be an effective strategy for improving the retention of endothelial cells within tissue engineered vascular grafts, which may in turn improve their clinical performance.

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Tissue Development, Repair, and Remodeling

Thiriet

2012

Tissue Functioning and Remodeling in the Circulatory and Ventilatory Systems

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Engineering blood vessels by gene and cell therapy

Cited by 7 publications

References 97 publications

Improved Patency of ePTFE Grafts as a Hemodialysis Access Site by Seeding Autologous Endothelial Cells Expressing Fibulin-5 and VEGF

Improved Patency of ePTFE Grafts as a Hemodialysis Access Site by Seeding Autologous Endothelial Cells Expressing Fibulin-5 and VEGF

Enhancement of Endothelial Cell Retention on ePTFE Vascular Constructs by siRNA-Mediated SHP-1 or SHP-2 Gene Silencing

Tissue Development, Repair, and Remodeling

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