人肾近端小管功能微生理模型的开发。
Development of a microphysiological model of human kidney proximal tubule function.
作者信息
Weber Elijah J, Chapron Alenka, Chapron Brian D, Voellinger Jenna L, Lidberg Kevin A, Yeung Catherine K, Wang Zhican, Yamaura Yoshiyuki, Hailey Dale W, Neumann Thomas, Shen Danny D, Thummel Kenneth E, Muczynski Kimberly A, Himmelfarb Jonathan, Kelly Edward J
机构信息
Department of Pharmaceutics, University of Washington, Seattle, Washington, USA.
Department of Pharmacy, University of Washington, Seattle, Washington, USA; Kidney Research Institute, University of Washington, Seattle, Washington, USA.
出版信息
Kidney Int. 2016 Sep;90(3):627-37. doi: 10.1016/j.kint.2016.06.011.
The kidney proximal tubule is the primary site in the nephron for excretion of waste products through a combination of active uptake and secretory processes and is also a primary target of drug-induced nephrotoxicity. Here, we describe the development and functional characterization of a 3-dimensional flow-directed human kidney proximal tubule microphysiological system. The system replicates the polarity of the proximal tubule, expresses appropriate marker proteins, exhibits biochemical and synthetic activities, as well as secretory and reabsorptive processes associated with proximal tubule function in vivo. This microphysiological system can serve as an ideal platform for ex vivo modeling of renal drug clearance and drug-induced nephrotoxicity. Additionally, this novel system can be used for preclinical screening of new chemical compounds prior to initiating human clinical trials.
肾近端小管是肾单位中通过主动摄取和分泌过程相结合来排泄废物的主要部位，也是药物诱导肾毒性的主要靶点。在此，我们描述了一种三维流动导向的人肾近端小管微生理系统的开发及其功能特性。该系统复制了近端小管的极性，表达适当的标记蛋白，展现出生物化学和合成活性，以及与体内近端小管功能相关的分泌和重吸收过程。这种微生理系统可作为肾药物清除和药物诱导肾毒性体外建模的理想平台。此外，这个新系统可用于在启动人体临床试验之前对新化合物进行临床前筛选。
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