Cardiac tissue engineering
Cardiac tissue engineering
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DOI：
10.1016/s0966-3274(02)00011-4
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发表时间：
2002-05-01
影响因子：
1.5
通讯作者：
Zimmermann, WH
中科院分区：
文献类型：
--
作者：
Eschenhagen, T;Didié, M;Zimmermann, WH
分化的心脏和非心脏细胞以及成体干细胞进入心脏的移植的最新进展表明，在心肌梗死期间发生的存活心肌细胞的不可逆损失可以至少部分地被替代。我们评估了一种替代方法，通过体外重建心脏组织移植物，并将其作为自发和连贯的收缩组织植入。为此，我们优化了一种从新生大鼠心肌细胞体外构建环形三维工程化心脏组织（EHT）的方法。当在器官浴中进行等长力测量时，电刺激的EHT表现出Frank-Starling行为，对细胞外钙增加的正性肌力反应，对异丙肾上腺素的正性肌力反应和负性肌力反应，以及对毒蕈碱激动剂卡巴胆碱的负性肌力反应（“增强拮抗”）。最大钙浓度下的抽搐张力为1-2 mN/mm（2）。重要的是，被动（静息）张力较低，在基础钙水平下产生的主动/被动张力比约为1.5，在最大钙水平下约为14。在形态学上，EHT代表了心肌细胞的高度互连的三维网络，类似于松散的心脏组织，具有高比例的双核心肌细胞、强伊红染色和细长的位于中心的核。电子显微镜显示发达的肌节结构、T-小管、SR囊泡、T-小管-SR-连接、所有类型的细胞间连接结构和基底膜。因此，EHT包括完整的心室心肌的功能和形态学特性。EHTs在Fischer 344大鼠腹膜中的首次植入实验表明，EHTs存活至少14天，维持分化的心肌细胞网络，并且强烈血管化。因此，EHT可以作为一种新的组织替代方法的材料。(C)2002 Elsevier Science B. V.保留所有权利。
Recent progress in implantations of differentiated cardiac and non-cardiac cells as well as adult stem cells into the heart suggests that the irreversible loss of viable cardiac myocytes that occurs during myocardial infarction can be at least partly substituted. We evaluated an alternative approach by reconstituting cardiac tissue grafts in vitro and implanting them as spontaneously and coherently contracting tissues. For this purpose we have optimized a method to generate ring-shaped three-dimensional engineered heart tissue (EHT) in vitro from neonatal rat cardiac myocytes. When subjected to isometric force measurements in organ baths, electrically stimulated EHTs exhibit a Frank-Starling behavior, a positive inotropic response to increases in extracellular calcium, a positive inotropic and lusitropic response to isoprenaline, and a negative inotropic response to the muscarinic agonist carbachol ('accentuated antagonism'). Twitch tension under maximal calcium amounts to 1-2 mN/mm(2). Importantly, passive (resting) tension is low, yielding a ratio of active/passive tension of approximately 1.5 under basal and 14 under maximal calcium. Morphologically, EHTs represent a highly interconnected three-dimensional network of cardiac myocytes resembling loose cardiac tissue with a high fraction of binucleated cardiac myocytes, strong eosin staining and elongated centrally located nuclei. Electron microscopy demonstrated well developed sarcomeric structures, T-tubules, SR vesicles, T-tubule-SR-junctions, all types of intercellular connective structures, and a basement membrane. Thus, EHTs comprise functional and morphological properties of intact, ventricular myocardium. First implantation experiments of EHTs in the peritoneum of Fischer 344 rats showed that EHTs survived for at least 14 days, maintained a network of differentiated cardiac myocytes, and were strongly vascularzed. Thus, EHTs may serve as material for a novel tissue replacement approach. (C) 2002 Elsevier Science B.V. All rights reserved.