Central European Institute of Technology, Masaryk University, Kamenice 5, 62500 Brno, Czech Republic; International Clinical Research Centre of Saint Anne Hospital Brno, Pekarska 53, 60200 Brno, Czech Republic; Department of Informatics, Bioengineering Robotics and Systems Engineering, University of Genova, Via All'Opera Pia, 13, 16145 Genova, Italy.
Central European Institute of Technology, Masaryk University, Kamenice 5, 62500 Brno, Czech Republic.
Biosens Bioelectron. 2019 Jan 15;124-125:129-135. doi: 10.1016/j.bios.2018.10.021. Epub 2018 Oct 16.
Cardiomyocytes (CM) placed on microelectrode array (MEA) were simultaneously probed with cantilever from atomic force microscope (AFM) system. This electric / nanomechanical combination in real time recorded beating force of the CMs cluster and the triggering electric events. Such "organ-on-a-chip" represents a tool for drug development and disease modeling. The human pluripotent stem cells included the WT embryonic line CCTL14 and the induced dystrophin deficient line reprogrammed from fibroblasts of a patient affected by Duchenne Muscular Dystrophy (DMD, complete loss of dystrophin expression). Both were differentiated to CMs and employed with the AFM/MEA platform for diseased CMs' drug response testing and DMD characterization. The dependence of cardiac parameters on extracellular Ca was studied. The differential evaluation explained the observed effects despite variability of biological samples. The β-adrenergic stimulation (isoproterenol) and antagonist trials (verapamil) addressed ionotropic and chronotropic cell line-dependent features. For the first time, a distinctive beating-force relation for DMD CMs was measured on the 3D cardiac in vitro model.
将心肌细胞 (CM) 置于微电极阵列 (MEA) 上，同时用原子力显微镜 (AFM) 系统的悬臂进行探测。这种实时的电/纳力学组合记录了心肌细胞簇的跳动力和触发电事件。这种“芯片上的器官”代表了一种用于药物开发和疾病建模的工具。人类多能干细胞包括 WT 胚胎系 CCTL14 和从患有杜氏肌营养不良症 (DMD，完全缺乏肌营养不良蛋白表达) 的患者的成纤维细胞重新编程的诱导型肌营养不良蛋白缺陷系。两者均分化为心肌细胞，并在 AFM/MEA 平台上用于病变心肌细胞的药物反应测试和 DMD 特征分析。研究了心脏参数对外界 Ca 的依赖性。尽管存在生物学样本的变异性，但差异化评估解释了观察到的效果。β-肾上腺素能刺激 (异丙肾上腺素) 和拮抗剂试验 (维拉帕米) 针对离子型和变时性细胞系依赖性特征。这是首次在 3D 心脏体外模型上测量了 DMD 心肌细胞的独特跳动力关系。
