A pumpless liver-on-a-chip for drug hepatotoxicity analysis,Analyst

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A pumpless liver-on-a-chip for drug hepatotoxicity analysis
Analyst ( IF 3.6 ) Pub Date : 2024-07-25 , DOI: 10.1039/d4an00602j
Dian Jiao ₁ , Lan Xie _{2,

3} , Wanli Xing _{2,

3}

Affiliation

This study presents the development and validation of an innovative microfluidic liver-on-a-chip device utilizing gravity-driven perfusion for the evaluation of drug hepatotoxicity. This research involved the construction of a hydrogel-based coculture chip that integrates liver parenchymal and stellate cells within a tri-channel configuration. The assembly and operation of the liver-on-a-chip and its accompanying custom rocker were straightforward. The cells in the chip maintained high viability and continuously synthesized liver albumin over extended culture durations. Acetaminophen (APAP), a hepatic injury-inducing drug, was utilized as a positive control in hepatic toxicity assays on the chip. The liver chip exhibited hepatotoxic responses comparable to those observed in 2D models. Furthermore, in this study we evaluated the effects of two plant-derived natural compounds, aristolochic acid I (AA) and its analog aristolactam AII (AL), in both 2D cell models and the liver-on-a-chip system. AA, known for its hepatorenal toxicity, was observed to cause hepatotoxicity in both the 2D models and on the chip. The flow cytometry and mRNA sequencing results confirmed the propensity of these compounds to induce liver cell apoptosis. Notably, AL, previously considered nontoxic, provoked a significant decrease in the hepatic functionality marker albumin exclusively in the liver chip but not in 2D models, indicating the liver chip's enhanced sensitivity to toxic substances. In summary, this pumpless liver-on-a-chip is a simple yet powerful tool for drug hepatotoxicity studies.

中文翻译：

用于药物肝毒性分析的无泵肝脏芯片

本研究介绍了一种创新的微流控肝脏芯片装置的开发和验证，该装置利用重力驱动灌注来评估药物的肝毒性。这项研究涉及构建基于水凝胶的共培养芯片，该芯片将肝实质细胞和星状细胞集成在三通道配置中。芯片肝脏及其随附的定制摇杆的组装和操作非常简单。芯片中的细胞在延长的培养时间内保持高活力并持续合成肝白蛋白。对乙酰氨基酚（APAP）是一种引起肝损伤的药物，被用作芯片上肝毒性测定的阳性对照。肝脏芯片表现出与二维模型中观察到的肝毒性反应相当的反应。此外，在这项研究中，我们评估了两种植物源性天然化合物马兜铃酸 I (AA) 及其类似物马兜铃内酰胺 AII (AL) 在 2D 细胞模型和肝脏芯片系统中的作用。 AA 以其肝肾毒性而闻名，在 2D 模型和芯片上均观察到会引起肝毒性。流式细胞术和mRNA测序结果证实了这些化合物诱导肝细胞凋亡的倾向。值得注意的是，以前被认为无毒的 AL 仅在肝脏芯片中引起肝功能标记物白蛋白显着下降，而在 2D 模型中则不然，这表明肝脏芯片对有毒物质的敏感性增强。总之，这种无泵肝脏芯片是药物肝毒性研究的一种简单而强大的工具。

更新日期：2024-07-25

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