Engineered heart tissue: a novel tool to study the ischemic changes of the heart in vitro.
Engineered heart tissue: a novel tool to study the ischemic changes of the heart in vitro.
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DOI：
10.1371/journal.pone.0009275
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发表时间：
2010-02-17
期刊：
影响因子：
3.7
通讯作者：
Sato T
中科院分区：
文献类型：
--
作者：
Katare RG;Ando M;Kakinuma Y;Sato T
了解任何疾病模式的基本机制和预防主要取决于成功的实验模型的开发。近年来，工程化心脏组织（EHT）已被证明是实验移植的有用工具。在这里，我们证明了一个新的功能，自发收缩EHT作为一个实验模型，在研究急性缺血引起的变化在体外。EHT通过混合从新生大鼠分离的心肌细胞并在环形支架中培养5天来构建。随后在孵育下机械拉伸EHT再一周。用环孢霉素A（CsA）和乙酰胆碱（ACh）等细胞保护剂处理后，将发育完全的EHT在1%O2下缺氧6小时。在培养过程中，EHT开始显示自发收缩，在机械拉伸后变得更加同步。这通过机械拉伸后间隙连接蛋白连接蛋白43的表达增加和使用光学映射系统的动作电位记录改善来证实。当受到缺氧，EHT表现出传导缺陷，连接蛋白-43去磷酸化，下调细胞存活蛋白相同的成人心脏。这些影响被抑制治疗EHT与细胞保护剂。在缺氧条件下，EHT的反应类似于成人心肌，从而使EHT成为一个有前途的材料，用于研究心脏功能的体外。
Understanding the basic mechanisms and prevention of any disease pattern lies mainly on development of a successful experimental model. Recently, engineered heart tissue (EHT) has been demonstrated to be a useful tool in experimental transplantation. Here, we demonstrate a novel function for the spontaneously contracting EHT as an experimental model in studying the acute ischemia-induced changes in vitro. EHT was constructed by mixing cardiomyocytes isolated from the neonatal rats and cultured in a ring-shaped scaffold for five days. This was followed by mechanical stretching of the EHT for another one week under incubation. Fully developed EHT was subjected to hypoxia with 1% O2 for 6 hours after treating them with cell protective agents such as cyclosporine A (CsA) and acetylcholine (ACh). During culture, EHT started to show spontaneous contractions that became more synchronous following mechanical stretching. This was confirmed by the increased expression of gap junctional protein connexin 43 and improved action potential recordings using an optical mapping system after mechanical stretching. When subjected to hypoxia, EHT demonstrated conduction defects, dephosphorylation of connexin-43, and down-regulation of cell survival proteins identical to the adult heart. These effects were inhibited by treating the EHT with cell protective agents. Under hypoxic conditions, the EHT responds similarly to the adult myocardium, thus making EHT a promising material for the study of cardiac functions in vitro.
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影响因子：
37.8
作者：
Ando, M;Katare, RG;Sato, T
通讯作者：
Sato, T
影响因子：
20.1
作者：
Zimmermann, WH;Schneiderbanger, K;Eschenhagen, T
通讯作者：
Eschenhagen, T
影响因子：
20.1
作者：
PFEFFER, MA;PFEFFER, JM;BRAUNWALD, E
通讯作者：
BRAUNWALD, E
影响因子：
6.4
作者：
Kaully, Tamar;Kaufman-Francis, Keren;Levenberg, Shulamit
通讯作者：
Levenberg, Shulamit
DOI：
10.1073/pnas.0908381106
发表时间：
2009-09-29
影响因子：
11.1
作者：
Stevens, K. R.;Kreutziger, K. L.;Murry, C. E.
通讯作者：
Murry, C. E.