Nieskens Tom T G, Wilmer Martijn J
Department of Pharmacology and Toxicology, Radboud Institute for Molecular Life Science, Radboud University Medical Center, Nijmegen, The Netherlands.
Department of Pharmacology and Toxicology, Radboud Institute for Molecular Life Science, Radboud University Medical Center, Nijmegen, The Netherlands.
Eur J Pharmacol. 2016 Nov 5;790:46-56. doi: 10.1016/j.ejphar.2016.07.018. Epub 2016 Jul 9.
The renal proximal tubule epithelium is responsible for active secretion of endogenous and exogenous waste products from the body and simultaneous reabsorption of vital compounds from the glomerular filtrate. The complexity of this transport machinery makes investigation of processes such as tubular drug secretion a continuous challenge for researchers. Currently available renal cell culture models often lack sufficient physiological relevance and reliability. Introducing complex biological culture systems in a 3D microfluidic design improves the physiological relevance of in vitro renal proximal tubule epithelium models. Organ-on-a-chip technology provides a promising alternative, as it allows the reconstruction of a renal tubule structure. These microfluidic systems mimic the in vivo microenvironment including multi-compartmentalization and exposure to fluid shear stress. Increasing data supports that fluid shear stress impacts the phenotype and functionality of proximal tubule cultures, for which we provide an extensive background. In this review, we discuss recent developments of kidney-on-a-chip platforms with current and future applications. The improved proximal tubule functionality using 3D microfluidic systems is placed in perspective of investigating cellular signalling that can elucidate mechanistic aberrations involved in drug-induced kidney toxicity.
肾近端小管上皮负责从体内主动分泌内源性和外源性废物，并同时从肾小球滤液中重吸收重要化合物。这种转运机制的复杂性使得研究诸如肾小管药物分泌等过程对研究人员来说一直是一项挑战。目前可用的肾细胞培养模型往往缺乏足够的生理相关性和可靠性。在三维微流控设计中引入复杂的生物培养系统可提高体外肾近端小管上皮模型的生理相关性。芯片器官技术提供了一种很有前景的替代方法，因为它可以重建肾小管结构。这些微流控系统模拟体内微环境，包括多隔室化和暴露于流体剪切应力。越来越多的数据表明，流体剪切应力会影响近端小管培养物的表型和功能，对此我们提供了广泛的背景信息。在这篇综述中，我们讨论了芯片肾脏平台的最新进展及其当前和未来的应用。从研究细胞信号传导的角度来看，利用三维微流控系统改善近端小管功能，这可以阐明药物性肾毒性所涉及的机制异常。
