A completely biological tissue-engineered human blood vessel
A completely biological tissue-engineered human blood vessel
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DOI：
10.1096/fasebj.12.1.47
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发表时间：
1998-01-01
期刊：
影响因子：
4.8
通讯作者：
Auger, FA
中科院分区：
文献类型：
--
作者：
L'Heureux, N;Pâquet, S;Auger, FA
机械挑战组织工程器官，如血管，传统上依赖于合成或改性生物材料的结构支持。在这份报告中，我们提出了一种新的方法来组织工程血管（TEBV）的生产，这是完全基于使用培养的人类细胞，即，而不需要任何合成或外源性生物材料。人血管平滑肌细胞（SMC）与抗坏血酸培养产生一个有凝聚力的细胞片。将该片材放置在管状支撑物周围以产生容器的介质。将类似的人成纤维细胞片包裹在培养基周围以提供外膜。成熟后，移除肾小管支持物，并将内皮细胞接种在管腔中。这种TEBV具有明确的三层组织和许多细胞外基质蛋白，包括弹性蛋白。在这种环境中，SMC重新表达结蛋白，一种已知在标准培养条件下丢失的分化标记物。内皮表达血管性血友病因子，掺入乙酰化LDL，产生PGI（2），并在体外强烈抑制血小板粘附。完整血管的爆破强度超过2000 mmHg。这是第一个完全生物的TEBV，显示出与人类血管相当的爆破强度。在犬模型中的短期移植实验证明了良好的操作性和可缝合性特征。总之，这些结果表明，这种新技术可以产生完全符合移植基本要求的生物血管：高爆破强度，积极的手术处理和功能性内皮。
Mechanically challenged tissue-engineered organs, such as blood vessels, traditionally relied on synthetic or modified biological materials for structural support. In this report, we present a novel approach to tissue-engineered blood vessel (TEBV) production that is based exclusively on the use of cultured human cells, i.e., without any synthetic or exogenous biomaterials. Human vascular smooth muscle cells (SMC) cultured with ascorbic acid produced a cohesive cellular sheet. This sheet was placed around a tubular support to produce the media of the vessel. A similar sheet of human fibroblasts was wrapped around the media to provide the adventitia. After maturation, the tubular support was removed and endothelial cells were seeded in the lumen. This TEBV featured a well-defined, three-layered organization and numerous extracellular matrix proteins, including elastin. In this environment, SMC reexpressed desmin, a differentiation marker known to be lost under standard culture conditions. The endothelium expressed von Willebrand factor, incorporated acetylated LDL, produced PGI(2), and strongly inhibited platelet adhesion in vitro. The complete vessel had a burst strength over 2000 mmHg. This is the first completely biological TEBV to display a burst strength comparable to that of human vessels. Short-term grafting experiment in a canine model demonstrated good handling and suturability characteristics. Taken together, these results suggest that this novel technique can produce completely biological vessels fulfilling the fundamental requirements for grafting: high burst strength, positive surgical handling, and a functional endothelium.