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Mol Ther ; 26(7): 1660-1668, 2018 07 05.
Artigo em Inglês | MEDLINE | ID: mdl-29703700

RESUMO

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.


Assuntos
Proteínas de Ligação ao Cálcio/metabolismo , Células Endoteliais/citologia , Células Endoteliais/metabolismo , Transplantes/metabolismo , Fatores de Crescimento do Endotélio Vascular/metabolismo , Animais , Prótese Vascular , Artérias Carótidas/citologia , Artérias Carótidas/metabolismo , Endotélio Vascular/citologia , Endotélio Vascular/metabolismo , Veias Jugulares/citologia , Veias Jugulares/metabolismo , Diálise Renal/métodos , Suínos , Transplantes/citologia
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