Stancescu Maria, Molnar Peter, McAleer Christopher W, McLamb William, Long Christopher J, Oleaga Carlota, Prot Jean-Matthieu, Hickman James J
NanoScience Technology Center, University of Central Florida, 12424 Research Parkway, Suite 400, Orlando, FL 32826, USA.
Department of Zoology, University of West Hungary, Szombathely H-9700, Hungary; Biomedical Engineering, Cornell University, Department of Biomedical Engineering, 115 Weill Hall, Ithaca, NY 14853, USA.
Biomaterials. 2015 Aug;60:20-30. doi: 10.1016/j.biomaterials.2015.04.035. Epub 2015 May 14.
This article details the construction and testing of a phenotypic assay system that models in vivo cardiac function in a parallel in vitro environment with human stem cell derived cardiomyocytes. The major determinants of human whole-heart function were experimentally modeled by integrating separate 2D cellular systems with BioMicroelectromechanical Systems (BioMEMS) constructs. The model features a serum-free defined medium to enable both acute and chronic evaluation of drugs and toxins. The integration of data from both systems produced biologically relevant predictions of cardiac function in response to varying concentrations of selected drugs. Sotalol, norepinephrine and verapamil were shown to affect the measured parameters according to their specific mechanism of action, in agreement with clinical data. This system is applicable for cardiac side effect assessment, general toxicology, efficacy studies, and evaluation of in vitro cellular disease models in body-on-a-chip systems.
本文详细介绍了一种表型分析系统的构建和测试，该系统在体外环境中利用人类干细胞衍生的心肌细胞对体内心脏功能进行建模。通过将独立的二维细胞系统与生物微机电系统（BioMEMS）构建体相结合，对人类全心功能的主要决定因素进行了实验建模。该模型采用无血清限定培养基，能够对药物和毒素进行急性和慢性评估。两个系统的数据整合产生了针对不同浓度所选药物的心脏功能的生物学相关预测。索他洛尔、去甲肾上腺素和维拉帕米根据其特定作用机制显示会影响测量参数，这与临床数据一致。该系统适用于心脏副作用评估、一般毒理学、疗效研究以及芯片上人体系统中体外细胞疾病模型的评估。
