Please use this identifier to cite or link to this item: https://doi.org/10.1038/s41598-017-13848-5
Title: A perfusion incubator liver chip for 3D cell culture with application on chronic hepatotoxicity testing
Authors: Yu, F
Deng, R
Hao Tong, W 
Huan, L
Chan Way, N
Islambadhan, A
Iliescu, C 
Yu, H 
Keywords: animal
cell culture technique
cell survival
cytology
devices
drug effect
lab on a chip
liver
liver cell
male
mass fragmentography
perfusion
procedures
rat
toxicity testing
Wistar rat
Animals
Cell Culture Techniques
Cell Survival
Gas Chromatography-Mass Spectrometry
Hepatocytes
Lab-On-A-Chip Devices
Liver
Male
Perfusion
Rats
Rats, Wistar
Toxicity Tests, Chronic
Issue Date: 2017
Publisher: Nature Publishing Group
Citation: Yu, F, Deng, R, Hao Tong, W, Huan, L, Chan Way, N, Islambadhan, A, Iliescu, C, Yu, H (2017). A perfusion incubator liver chip for 3D cell culture with application on chronic hepatotoxicity testing. Scientific Reports 7 (1) : 14528. ScholarBank@NUS Repository. https://doi.org/10.1038/s41598-017-13848-5
Abstract: Liver chips have been developed to recapitulate in vivo physiological conditions to enhance hepatocyte functions for assessing acute responses to drugs. To develop liver chips that can assess repeated dosing chronic hepatotoxicity, we need to ensure that hepatocyte functions be maintained at constant values over two weeks in stable culture conditions of sterility, temperature, pH, fluidic-flow of culture media and drugs. We have designed a perfusion-incubator-liver-chip (PIC) for 3D cell culture, that assures a tangential flow of the media over the spheroids culture. Rat hepatocyte spheroids constrained between a cover glass and a porous-ultrathin Parylene C membrane experienced optimal mass transfer and limited shear stress from the flowing culture media; maintained cell viability over 24 days. Hepatocyte functions were significantly improved and maintained at constant values (urea, albumin synthesis, and CYP450 enzyme activities) for 14 days. The chip act as an incubator, having 5% CO2 pressure-driven culture-media flow, on-chip heater and active debubbler. It operates in a biosafety cabinet, thus minimizing risk of contamination. The chronic drug response to repeated dosing of Diclofenac and Acetaminophen evaluated in PIC were more sensitive than the static culture control. © 2017 The Author(s).
Source Title: Scientific Reports
URI: https://scholarbank.nus.edu.sg/handle/10635/174389
ISSN: 2045-2322
DOI: 10.1038/s41598-017-13848-5
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