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芯片肾技术用于药物诱导的肾毒性筛选。

Kidney-on-a-Chip Technology for Drug-Induced Nephrotoxicity Screening.

机构信息

Department of Pharmacology and Toxicology, Radboudumc, PO Box 9101, Nijmegen, HB 6500 The Netherlands.

MIMETAS BV, JH Oortweg 19, Leiden, CH, 2333 The Netherlands.

出版信息

Trends Biotechnol. 2016 Feb;34(2):156-170. doi: 10.1016/j.tibtech.2015.11.001. Epub 2015 Dec 18.

Abstract

Improved model systems to predict drug efficacy, interactions, and drug-induced kidney injury (DIKI) are crucially needed in drug development. Organ-on-a-chip technology is a suitable in vitro system because it reproduces the 3D microenvironment. A kidney-on-a-chip can mimic the structural, mechanical, transport, absorptive, and physiological properties of the human kidney. In this review we address the application of state-of-the-art microfluidic culturing techniques, with a focus on culturing kidney proximal tubules, that are promising for the detection of biomarkers that predict drug interactions and DIKI. We also discuss high-throughput screening and the challenges for in vitro to in vivo extrapolation (IVIVE) that will need to be overcome for successful implementation.

摘要

在药物开发中,迫切需要改进的模型系统来预测药物疗效、相互作用和药物引起的肾损伤 (DIKI)。器官芯片技术是一种合适的体外系统,因为它可以复制 3D 微环境。肾芯片可以模拟人类肾脏的结构、机械、运输、吸收和生理特性。在这篇综述中,我们讨论了最先进的微流控培养技术的应用,重点是培养肾近端小管,这对于检测预测药物相互作用和 DIKI 的生物标志物具有很大的潜力。我们还讨论了高通量筛选和体外向体内外推 (IVIVE) 的挑战,这些挑战需要克服才能成功实施。

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