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Issue 17, 2014
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Hepatic organoids for microfluidic drug screening

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Abstract

We introduce the microfluidic organoids for drug screening (MODS) platform, a digital microfluidic system that is capable of generating arrays of individually addressable, free-floating, three-dimensional hydrogel-based microtissues (or ‘organoids’). Here, we focused on liver organoids, driven by the need for early-stage screening methods for hepatotoxicity that enable a “fail early, fail cheaply” strategy in drug discovery. We demonstrate that arrays of hepatic organoids can be formed from co-cultures of HepG2 and NIH-3T3 cells embedded in hydrogel matrices. The organoids exhibit fibroblast-dependent contractile behaviour, and their albumin secretion profiles and cytochrome P450 3A4 activities are better mimics of in vivo liver tissue than comparable two-dimensional cell culture systems. As proof of principle for screening, MODS was used to generate and analyze the effects of a dilution series of acetaminophen on apoptosis and necrosis. With further development, we propose that the MODS platform may be a cost-effective tool in a “fail early, fail cheaply” paradigm of drug development.

Graphical abstract: Hepatic organoids for microfluidic drug screening

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Publication details

The article was received on 04 May 2014, accepted on 20 Jun 2014 and first published on 02 Jul 2014


Article type: Paper
DOI: 10.1039/C4LC00531G
Citation: Lab Chip, 2014,14, 3290-3299
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    Hepatic organoids for microfluidic drug screening

    S. H. Au, M. D. Chamberlain, S. Mahesh, M. V. Sefton and A. R. Wheeler, Lab Chip, 2014, 14, 3290
    DOI: 10.1039/C4LC00531G

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