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Two-Dimensional Culture Systems to Enable Mechanics-Based Assays for Stem Cell-Derived Cardiomyocytes
Experimental Mechanics ( IF 2.0 ) Pub Date : 2019-01-29 , DOI: 10.1007/s11340-019-00473-8
J Notbohm 1, 2 , B N Napiwocki 2, 3 , W J deLange 4 , A Stempien 2, 3 , A Saraswathibhatla 1 , R J Craven 2, 3 , M R Salick 3, 5 , J C Ralphe 4 , W C Crone 1, 2, 3, 5
Affiliation  

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.

中文翻译:


二维培养系统可对干细胞衍生的心肌细胞进行基于力学的测定



控制良好的二维细胞培养系统推进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创新平台。这些细胞培养系统已经变得更加先进,以便提供和量化模拟体内条件环境的适当生物力学和生化线索。在这里,我们提出了一种创新的二维细胞培养系统,用于研究人类干细胞衍生的心肌细胞,心脏的肌肉细胞负责将血液泵送到全身。我们设计了二维细胞培养平台来控制细胞内特征,以产生类似成人的心肌细胞组织,其连接性和各向异性传导与天然心脏相当,并将其与光学显微镜相结合,以量化细胞-细胞和细胞-基质的机械相互作用。我们展示了对单个细胞内、相邻细胞之间以及细胞与其周围矩阵之间发生的力和位移的测量。该系统具有广泛的潜力,可以扩展我们对组织生理学的理解,对于研究机械活动的心脏具有特别的优势。此外,该技术在筛选潜在药物的功效和测试毒性方面应该具有价值。
更新日期:2019-01-29
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