期刊
LAB ON A CHIP
卷 14, 期 17, 页码 3290-3299出版社
ROYAL SOC CHEMISTRY
DOI: 10.1039/c4lc00531g
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资金
- Natural Sciences and Engineering Research Council of Canada (NSERC)
- Canadian Institutes of Health Research (CIHR)
- Ontario Research Excellence Fund
- Ontario Institute for Cancer Research (OICR)
- NSERC
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.
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