Fibrotic diseases are among the most serious health issues with severe burdens due to their chronic nature and a large number of patients suffering from the debilitating effects and long-term sequelae. Collagenase treatment is a nonsurgical option but has limited results. To date, there is no potent noninvasive solution for fibrosis. Part of the reason for this is the lack of appropriate in vitro live cell screening tools to assess the efficacy of new therapeutical agents. Here, we demonstrate the utility of a cell-based electrochemical impedance biosensor platform to screen the efficacy of potential antifibrotic compounds. The platform employs a label-free and noninvasive strategy to detect the progression of fibrosis and the potency of the antifibrotic molecules in real-time. The fundamental principle that governs this novel system is that dynamic changes in cell shape and adhesion during fibrosis can be measured accurately by monitoring the changes in the impedance. This is achieved by growing the cells on a transparent interdigitated indium tin oxide (ITO) electrodes. It was demonstrated by monitoring the efficacy of a model antifibrotic compound, PXS64, on cells collected from patients with Dupuytren’s contracture. We confirmed the validity of the developed biochemical impedance biosensor as an tool for in vitro screening of antifibrotic compounds and provided quantitative information on subcellular influences of the examined chemical molecules using correlative microscopy analyses that monitor the average cell area, cell morphology, and the amount and directionality of the deposited extracellular matrix protein collagen and measurement of cytosolic Ca²⁺ changes.

中文翻译：

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实时生物阻抗传感在人类原代细胞中的抗纤维化药物作用

纤维化疾病由于其慢性性质，是最严重的健康问题，并且负担沉重，并且使许多患者遭受虚弱的影响和长期的后遗症。胶原酶治疗是非手术选择，但效果有限。迄今为止，还没有有效的非侵入性纤维化解决方案。造成这种情况的部分原因是缺乏适当的体外方法活细胞筛选工具，以评估新型治疗剂的功效。在这里，我们演示了基于细胞的电化学阻抗生物传感器平台筛选潜在抗纤维化化合物功效的实用程序。该平台采用无标签，非侵入性策略，可实时检测纤维化的进展和抗纤维化分子的功效。控制这个新颖系统的基本原理是，通过监测阻抗的变化，可以准确地测量纤维化过程中细胞形状和粘附的动态变化。这可以通过在透明的叉指状铟锡氧化物（ITO）电极上生长电池来实现。通过监测模型抗纤维化化合物PXS64对从Dupuytren挛缩症患者收集的细胞的功效来证明这一点。使用相关显微镜分析对抗纤维化化合物进行体外筛选，并提供有关所检查化学分子的亚细胞影响的定量信息，以监测平均细胞面积，细胞形态，沉积的细胞外基质蛋白胶原蛋白的数量和方向以及胞浆Ca ^2的测量⁺变化。