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用于纳米颗粒肝毒性测试的微流控 3D 肝细胞芯片。

A microfluidic 3D hepatocyte chip for hepatotoxicity testing of nanoparticles.

机构信息

Center for Engineering in Medicine, Massachusetts General Hospital, Harvard Medical School, Shriners Hospitals, Boston, MA 02114, USA.

CAS Key Laboratory of Cryogenics, Technical Institute of Physics and Chemistry, Chinese Academy of Sciences, Beijing, PR China.

出版信息

Nanomedicine (Lond). 2019 Aug;14(16):2209-2226. doi: 10.2217/nnm-2019-0086. Epub 2019 Jun 10.

Abstract

To develop a practical microfluidic 3D hepatocyte chip for hepatotoxicity testing of nanoparticles using proof of concept studies providing first results of the potential hepatotoxicity of superparamagnetic iron oxide nanoparticles (SPION) under microfluidic conditions. A microfluidic 3D hepatocyte chip with three material layers, which contains primary rat hepatocytes, has been fabricated and tested using different concentrations (50, 100 and 200 μg/ml) of SPION in 3-day (short-term) and 1-week (long-term) cultures. Compared with standard well plates, the hepatocyte chip with flow provided comparable viability and significantly higher liver-specific functions, up to 1 week. In addition, the chip recapitulates the key physiological responses in the hepatotoxicity of SPION. Thus, the developed 3D hepatocyte chip is a robust and highly sensitive platform for investigating hepatotoxicity profiles of nanoparticles.

摘要

为了开发一种实用的微流控 3D 肝细胞芯片,用于纳米颗粒的肝毒性测试,通过概念验证研究提供超顺磁氧化铁纳米颗粒(SPION)在微流控条件下潜在肝毒性的初步结果。已经制造和测试了具有三个材料层的微流控 3D 肝细胞芯片,其中包含原代大鼠肝细胞,使用不同浓度(50、100 和 200μg/ml)的 SPION 在 3 天(短期)和 1 周(长期)培养中进行。与标准培养板相比,提供流动的肝细胞芯片具有相当的活力和显著更高的肝脏特异性功能,长达 1 周。此外,该芯片再现了 SPION 肝毒性的关键生理反应。因此,开发的 3D 肝细胞芯片是一种强大且高度敏感的平台,可用于研究纳米颗粒的肝毒性特征。

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