Department of Pharmacology and Toxicology, Radboudumc, PO Box 9101, Nijmegen, HB 6500 The Netherlands.
MIMETAS BV, JH Oortweg 19, Leiden, CH, 2333 The Netherlands.
Trends Biotechnol. 2016 Feb;34(2):156-170. doi: 10.1016/j.tibtech.2015.11.001. Epub 2015 Dec 18.
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.
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。