评估非临床毒性的微生理系统。

Kirk P Van Ness, Shih-Yu Chang, Elijah J Weber, Danielle Zumpano, David L Eaton, Edward J Kelly
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引用次数: 19

摘要

在药物开发过程中,肝脏和肾脏是关键的毒性靶器官,因为它们通常承担着药物运输和代谢的负担。在传统的体外二维培养系统中培养的原代肝细胞和近端小管上皮细胞不能维持转运和代谢功能,因此限制了它们在非临床毒理学研究中的应用。我们开发了一种肾脏和肝脏微生理系统(MPS)平台,该平台使用市售的MPS设备作为我们方法的核心细胞培养平台。我们描述了分离和繁殖人类近端上皮细胞的方案,以及如何播种和培养肾脏MPS来概括人类近端小管。我们提出了两种在MPS中培养肝细胞的方法,以及将肾脏MPS连接到肝脏MPS所需的步骤。©2017 by John Wiley & Sons, Inc。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Microphysiological Systems to Assess Nonclinical Toxicity.

Microphysiological Systems to Assess Nonclinical Toxicity.

Microphysiological Systems to Assess Nonclinical Toxicity.

Microphysiological Systems to Assess Nonclinical Toxicity.

The liver and the kidney are key toxicity target organs during drug development campaigns, as they typically carry the burden of drug transport and metabolism. Primary hepatocytes and proximal tubule epithelial cells grown in traditional in vitro 2-D culture systems do not maintain transporter and metabolic functions, thus limiting their utility for nonclinical toxicology investigations. We have developed a renal and hepatic microphysiological system (MPS) platform that uses a commercially available MPS device as the core cell culture platform for our methodologies. We describe protocols for isolating and propagating human proximal epithelial cells and how to seed and culture a renal MPS to recapitulate the human proximal tubule. We present two methods to culture hepatocytes within an MPS and the steps required to connect a renal MPS to a liver MPS. © 2017 by John Wiley & Sons, Inc.

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