Two-Dimensional Culture Systems to Enable Mechanics-Based Assays for Stem Cell-Derived Cardiomyocytes
Two-Dimensional Culture Systems to Enable Mechanics-Based Assays for Stem Cell-Derived Cardiomyocytes
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DOI：
10.1007/s11340-019-00473-8
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发表时间：
2019-11-01
影响因子：
2.4
通讯作者：
Crone, W. C.
中科院分区：
文献类型：
--
作者：
Notbohm, J.;Napiwocki, B. N.;Crone, W. C.
控制良好的2D细胞培养系统促进了细胞生物学的基础研究，并为药物开发、毒性测试和诊断分析提供了创新的平台。这些细胞培养系统已经变得更加先进，以便提供并量化适当的生物力学和生化线索，以模拟体内存在的条件。在这里，我们提出了一种创新的2D细胞培养系统来研究人类干细胞来源的心肌细胞，心脏的肌肉细胞负责将血液输送到全身。我们设计了我们的2D细胞培养平台来控制细胞内的特征，以产生成体样的心肌细胞组织，具有与自然心脏相当的连通性和各向异性传导，并将其与光学显微镜相结合来量化细胞-细胞和细胞-基质的机械相互作用。我们展示了发生在单个细胞内、相邻细胞之间以及细胞与其周围基质之间的力和位移的测量。该系统对扩大我们对组织生理学的理解具有广阔的潜力，尤其对机械活动心脏的研究具有特殊的优势。此外，这项技术在筛选潜在药物的疗效和毒性测试方面应该被证明是有价值的。
Well-controlled 2D cell culture systems advance basic investigations in cell biology and provide innovative platforms for drug development, toxicity testing, and diagnostic assays. These cell culture systems have become more advanced in order to provide and to quantify the appropriate biomechanical and biochemical cues that mimic the milieu of conditions present in vivo. Here we present an innovative 2D cell culture system to investigate human stem cell-derived cardiomyocytes, the muscle cells of the heart responsible for pumping blood throughout the body. We designed our 2D cell culture platform to control intracellular features to produce adult-like cardiomyocyte organization with connectivity and anisotropic conduction comparable to the native heart, and combined it with optical microscopy to quantify cell-cell and cell-substrate mechanical interactions. We show the measurement of forces and displacements that occur within individual cells, between neighboring cells, and between cells and their surrounding matrix. This system has broad potential to expand our understanding of tissue physiology, with particular advantages for the study of the mechanically active heart. Furthermore, this technique should prove valuable in screening potential drugs for efficacy and testing for toxicity.