Real-Time Force and Frequency Analysis of Engineered Human Heart Tissue Derived from Induced Pluripotent Stem Cells Using Magnetic Sensing
Real-Time Force and Frequency Analysis of Engineered Human Heart Tissue Derived from Induced Pluripotent Stem Cells Using Magnetic Sensing
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DOI：
10.1089/ten.tec.2016.0257
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发表时间：
2016-10-01
影响因子：
3
通讯作者：
Sniadecki, Nathan J.
中科院分区：
文献类型：
--
作者：
Bielawski, Kevin S.;Leonard, Andrea;Sniadecki, Nathan J.
由人类多能干细胞衍生的心肌细胞制成的工程心脏组织已被用于心脏病理建模、筛选新疗法和提供替代心脏组织。目前的方法是通过抽动力和跳动频率来测量工程心脏组织的功能性能，通常是通过光学测量获得的。在本文中，我们描述了一种利用磁场传感来评估工程心脏组织抽动力和跳动频率的新方法，该方法可以同时测量多个组织。这些组织是悬浮在两个硅胶柱子之间的薄结构，其中一个柱子是刚性的，另一个是柔性的，并包含一个嵌入的磁铁。当组织收缩时，它会使柔性杆按其收缩力的比例弯曲。我们使用巨磁电阻（GMR）传感器测量了立柱的弯曲度，该传感器位于包含组织的24孔板下方。我们根据光学测量验证了GMR传感器读数的准确性。我们通过实时平行实验测试三种浓度异丙肾上腺素和维拉帕米对抽动力和跳动频率的影响，证明了我们方法的实用性和敏感性。该系统应可扩展到24孔格式之外，在组织工程环境中评估心肌细胞的收缩功能时能够实现更高的自动化。
Engineered heart tissues made from human pluripotent stem cell-derived cardiomyocytes have been used for modeling cardiac pathologies, screening new therapeutics, and providing replacement cardiac tissue. Current methods measure the functional performance of engineered heart tissue by their twitch force and beating frequency, typically obtained by optical measurements. In this article, we describe a novel method for assessing twitch force and beating frequency of engineered heart tissue using magnetic field sensing, which enables multiple tissues to be measured simultaneously. The tissues are formed as thin structures suspended between two silicone posts, where one post is rigid and another is flexible and contains an embedded magnet. When the tissue contracts it causes the flexible post to bend in proportion to its twitch force. We measured the bending of the post using giant magnetoresistive (GMR) sensors located underneath a 24-well plate containing the tissues. We validated the accuracy of the readings from the GMR sensors against optical measurements. We demonstrated the utility and sensitivity of our approach by testing the effects of three concentrations of isoproterenol and verapamil on twitch force and beating frequency in real-time, parallel experiments. This system should be scalable beyond the 24-well format, enabling greater automation in assessing the contractile function of cardiomyocytes in a tissue-engineered environment.