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.
journal_name
Sci Repjournal_title
Scientific reportsauthors
Yu F,Deng R,Hao Tong W,Huan L,Chan Way N,IslamBadhan A,Iliescu C,Yu Hdoi
10.1038/s41598-017-13848-5subject
Has Abstractpub_date
2017-11-06 00:00:00pages
14528issue
1issn
2045-2322pii
10.1038/s41598-017-13848-5journal_volume
7pub_type
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