Guiding endothelial progenitor cell tube formation using patterned fibronectin surfaces

Guiding endothelial progenitor cell tube formation using patterned fibronectin surfaces
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DOI:
10.1039/c0sm00233j
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发表时间:
2010-01-01
期刊:
影响因子:
3.4
通讯作者:
Gerecht, Sharon
Gerecht, Sharon
中科院分区:
化学2区
文献类型:
--
作者:
Dickinson, Laura E.;Moura, Matthew E.;Gerecht, Sharon

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工程血管网络是再生医学的一项关键举措。此外,在体外控制有组织的血管网络的形成可以促进它们在植入后与宿主脉管系统的快速和功能性整合。细胞外基质为内皮祖细胞(EPCs)分化和组装成管状结构提供了结构平台。我们证明,优化的,图案化的纤连蛋白表面引导人内皮祖细胞的有序粘附,维持内皮祖细胞对肿瘤坏死因子-α的反应性,支持其延长沿着培养期,并增强血管性血友病因子的表达。使用纤维蛋白凝胶作为三维环境允许单向链的组装和管状结构的形成。高分辨率分析显示了一个独特的管腔,以及众多的韦伯帕拉德机构和小窝,所有这些都表明在血管形态发生和血管生成过程中的典型进展。总而言之,这种方法使我们能够在体外设计组织良好的血管结构的形成。
Engineering vascular networks is a key initiative in regenerative medicine. Moreover, control over the formation of organized vascular networks in vitro may facilitate their rapid and functional integration with the host vasculature after implantation. The extracellular matrix provides a structural platform for endothelial progenitor cells (EPCs) to differentiate and assemble into a tubular structure. We demonstrate that optimized, patterned fibronectin surfaces guide the ordered adhesion of human EPCs, maintain EPC responsiveness to tumor necrosis factor-alpha, support their elongation along the culture period, and enhance von Willebrand factor expression. Using fibrin gel as the three-dimensional milieu allows the assembly of unidirectional chains and formation of tubular structures. High-resolution analysis shows a distinctive lumen, as well as numerous Weibel Palade bodies and caveolae, all indicating a typical progression in vascular morphogenesis and the angiogenic process. Altogether, this approach allows us to engineer the formation of well-organized vascular structures in vitro.