Heart/liver-on-a-chip as a model for the evaluation of cardiotoxicity induced by chemotherapies

Organs-on-a-chip Pub Date : 2021-11-01 DOI:10.1016/j.ooc.2021.100008

Pooneh Soltantabar , Erika L. Calubaquib , Ebrahim Mostafavi , Atefeh Ghazavi , Mihaela C. Stefan

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引用次数: 10

Abstract

Drug discovery faces challenges due to the lack of proper preclinical tests, including conventional cell cultures and animal studies. Organ-on-a-chip devices can mimic the whole-body response to therapeutics by fluidically connecting microscale cell cultures and generating a realistic model of human organs of interest. Here, we describe a pumpless heart/liver-on-a-chip (HLC) using the HepG2 hepatocellular carcinoma cells and H9c2 rat cardiomyocytes to reproduce the cardiotoxicity induced by doxorubicin (DOX) in vitro. Cell studies confirmed the high viability of both cells up to 5 days of culture in HLC. The developed device demonstrated more significant damage to heart cells within the HLC than conventional static 3D culture in the case of DOX treatment, which is because of exposure of cells to both the parent drug and its cardiotoxic metabolite, Doxorubicinol (DOXOL). Our designed HLC device represents a unique approach to assess the off-target toxicity of drugs and their metabolites, which will eventually improve current preclinical studies.

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心脏/肝脏芯片作为评估化疗引起的心脏毒性的模型

由于缺乏适当的临床前试验，包括传统的细胞培养和动物研究，药物发现面临挑战。器官芯片设备可以通过流体连接微尺度细胞培养来模拟人体对治疗的反应，并产生感兴趣的人体器官的现实模型。在这里，我们描述了一种无泵心脏/肝脏芯片(HLC)，使用HepG2肝癌细胞和H9c2大鼠心肌细胞在体外复制阿霉素(DOX)诱导的心脏毒性。细胞研究证实，两种细胞在hplc中培养5天后均具有较高的活力。在DOX治疗的情况下，该装置对HLC内的心脏细胞的损伤比传统的静态3D培养更显著，这是因为细胞暴露于母体药物及其心脏毒性代谢物DOXOL(阿霉素)。我们设计的高效液相色谱装置代表了一种独特的方法来评估药物及其代谢物的脱靶毒性，这将最终改善目前的临床前研究。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Organs-on-a-chip Analytical Chemistry, Biochemistry, Genetics and Molecular Biology (General), Cell Biology, Pharmacology, Toxicology and Pharmaceutics (General)

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审稿时长

125 days