Perfusion-decellularized matrix: using nature's platform to engineer a bioartificial heart
Perfusion-decellularized matrix: using nature's platform to engineer a bioartificial heart
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DOI：
10.1038/nm1684
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发表时间：
2008-02-01
期刊：
影响因子：
82.9
通讯作者：
Taylor, Doris A.
中科院分区：
文献类型：
--
作者：
Ott, Harald C.;Matthiesen, Thomas S.;Taylor, Doris A.
在美国，大约有3,000人正在等待捐赠的心脏;全世界有2200万人患有心力衰竭。生物人工心脏是移植或机械左心室支持的理论替代方案。产生生物人工心脏需要心脏结构、适当的细胞成分和泵功能的工程化。我们通过用洗涤剂进行冠状动脉灌注来脱细胞心脏，保留了底层的细胞外基质，并产生了无细胞的、可灌注的血管结构、有能力的无细胞瓣膜和完整的腔室几何结构。为了模拟心脏细胞的组成，我们用心脏细胞或内皮细胞重新构建这些结构。为了建立功能，我们在模拟心脏生理学的生物反应器中通过冠状动脉灌注维持8个构建体长达28天。到第4天，我们观察到肉眼可见的收缩。到第8天，在生理负荷和电刺激下，结构可以在改良的工作心脏制备中产生泵功能（相当于成人心脏功能的约2%或16周胎儿心脏功能的25%）。
About 3,000 individuals in the United States are awaiting a donor heart; worldwide, 22 million individuals are living with heart failure. A bioartificial heart is a theoretical alternative to transplantation or mechanical left ventricular support. Generating a bioartificial heart requires engineering of cardiac architecture, appropriate cellular constituents and pump function. We decellularized hearts by coronary perfusion with detergents, preserved the underlying extracellular matrix, and produced an acellular, perfusable vascular architecture, competent acellular valves and intact chamber geometry. To mimic cardiac cell composition, we reseeded these constructs with cardiac or endothelial cells. To establish function, we maintained eight constructs for up to 28 d by coronary perfusion in a bioreactor that simulated cardiac physiology. By day 4, we observed macroscopic contractions. By day 8, under physiological load and electrical stimulation, constructs could generate pump function (equivalent to about 2% of adult or 25% of 16-week fetal heart function) in a modified working heart preparation.