Blood outgrowth endothelial cells alter remodeling of completely biological engineered grafts implanted into the sheep femoral artery.

Blood outgrowth endothelial cells alter remodeling of completely biological engineered grafts implanted into the sheep femoral artery.
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DOI:
10.1007/s12265-013-9539-z
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发表时间:
2014-03
影响因子:
3.4
通讯作者:
Tranquillo, Robert T.
Tranquillo, Robert T.
中科院分区:
医学3区
文献类型:
--
作者:
Meier, Lee A.;Syedain, Zeeshan H.;Lahti, Matthew T.;Johnson, Sandra S.;Chen, Minna H.;Hebbel, Robert P.;Tranquillo, Robert T.

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组织工程血管移植物的血液相容性仍然是小直径血管移植物临床应用的主要障碍。在此,我们评估了在羊股动脉植入术之前,利用自体血液外生内皮细胞在完全生物脱细胞工程同种异体移植物上通过腔内播种形成内皮的可行性。该移植物直径4毫米,长2- 3厘米,由纤维蛋白凝胶在体外由绵羊真皮成纤维细胞在脱细胞前重塑成排列的组织管。植入造血内皮细胞的去细胞移植物(n=3)在植入1小时后保留了前所未有的(bbb95 %)单层覆盖度,并且在植入9周后(包括不进行抗凝治疗的最后一周)具有更大的内皮覆盖度、更小的壁厚和更多的基底膜,与对侧未植入种子的对照组相比。这些结果支持使用自体血液外生内皮细胞作为内皮细胞的可行来源,在成纤维细胞重塑的纤维蛋白制成的脱细胞工程同种异体移植物上创造具有生物功能的内皮。
Hemocompatibility of tissue-engineered vascular grafts remains a major hurdle to clinical utility for small-diameter grafts. Here we assessed the feasibility of using autologous blood outgrowth endothelial cells to create an endothelium via lumenal seeding on completely biological, decellularized engineered allografts prior to implantation in the sheep femoral artery. The 4-mm-diameter, 2- to 3-cm-long grafts were fabricated from fibrin gel remodeled into an aligned tissue tube in vitro by ovine dermal fibroblasts prior to decellularization. Decellularized grafts pre-seeded with blood outgrowth endothelial cells (n=3) retained unprecedented (>95 %) monolayer coverage 1 h post-implantation and had greater endothelial coverage, smaller wall thickness, and more basement membrane after 9-week implantation, including a final week without anti-coagulation therapy, compared with contralateral non-seeded controls. These results support the use of autologous blood outgrowth endothelial cells as a viable source of endothelial cells for creating an endothelium with biological function on decellularized engineered allografts made from fibroblast-remodeled fibrin.
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