Functional innervation of human induced pluripotent stem cell-derived cardiomyocytes by co-culture with sympathetic neurons developed using a microtunnel technique
Functional innervation of human induced pluripotent stem cell-derived cardiomyocytes by co-culture with sympathetic neurons developed using a microtunnel technique
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通过与微隧道技术开发的交感神经元共培养，对人诱导多能干细胞衍生的心肌细胞进行功能性神经支配
DOI：
10.1016/j.bbrc.2017.10.065
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发表时间：
2017
影响因子：
3.1
通讯作者：
Jimbo Yasuhiko
中科院分区：
文献类型：
--
作者：
Sakai Koji;Shimba Kenta;Ishizuka Kazuma;Yang Zhuonan;Oiwa Kosuke;Takeuchi Akimasa;Kotani Kiyoshi;Jimbo Yasuhiko
基于微电极阵列（MEA）的人类诱导多能干细胞来源的心肌细胞（hiPSCM）药物筛选是一种有效评估新候选人心律失常风险的有效临床前检测方法。此外，预测心律失常副作用的交感调节是一个重要的问题。虽然我们之前已经开发了一种基于mea的大鼠原代心肌细胞和交感神经元（rSNs）共培养系统，但尚不清楚这种共培养方法是否适用于开发和研究hiPSCMs的交感神经支配。在这项研究中，我们在MEA基质上开发了rsn和hipscm的共培养，并评估了功能连接。在不同频率和脉冲数的SNs刺激下，hiphscm的搏动间隔明显缩短，说明rSNs与hiphscm之间存在功能联系，以及时变效应对rSN活动模式的依赖性。这些结果表明，我们的共培养方法可以评估对hiPSCMs的交感作用，并将成为评估人类心脏组织中交感调节心脏毒性的有用工具。
Microelectrode array (MEA) based-drug screening with human induced pluripotent stem cell-derived cardiomyocytes (hiPSCM) is a potent pre-clinical assay for efficiently assessing proarrhythmic risks in new candidates. Furthermore, predicting sympathetic modulation of the proarrhythmic side-effects is an important issue. Although we have previously developed an MEA-based co-culture system of rat primary cardiomyocyte and sympathetic neurons (rSNs), it is unclear if this co-culture approach is applicable to develop and investigate sympathetic innervation of hiPSCMs. In this study, we developed a co-culture of rSNs and hiPSCMs on MEA substrate, and assessed functional connections. The inter-beat interval of hiPSCM was significantly shortened by stimulation in SNs depending on frequency and pulse number, indicating functional connections between rSNs and hiPSCM and the dependency of chronotropic effects on rSN activity pattern. These results suggest that our co-culture approach can evaluate sympathetic effects on hiPSCMs and would be a useful tool for assessing sympathetic modulated-cardiotoxicity in human cardiac tissue.