Journal
BIOTECHNOLOGY JOURNAL
Volume 14, Issue 7, Pages -Publisher
WILEY-V C H VERLAG GMBH
DOI: 10.1002/biot.201800347
Keywords
cytochrome P450; drug metabolism; hepatotoxicity; liver fibrosis; liver-on-a-chip; microfluidic systems; spheroids; steatosis
Funding
- Swedish Research Council [2015-02760, 2016-01153, 2016-01154]
- Strategic Research Programme in Diabetes at Karolinska Institutet
- Lennart Philipson Foundation
- Harald and Greta Jeansson Foundation
- ERC Advanced Grant HepaSphere [742020]
- European Research Council (ERC) [742020] Funding Source: European Research Council (ERC)
- Swedish Research Council [2015-02760] Funding Source: Swedish Research Council
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Recent research has shown that the maintenance of relevant liver functions ex vivo requires models in which the cells exhibit an in vivo-like phenotype, often achieved by reconstitution of appropriate cellular interactions. Multiple different models have been presented that differ in the cells utilized, media, and culture conditions. Furthermore, several technologically different approaches have been presented including bioreactors, chips, and plate-based systems in fluidic or static media constituting of chemically diverse materials. Using such models, the ability to predict drug metabolism, drug toxicity, and liver functionality have increased tremendously as compared to conventional in vitro models in which cells are cultured as 2D monolayers. Here, the authors highlight important considerations for microphysiological systems for primary hepatocyte culture, review current culture paradigms, and discuss their opportunities for studies of drug metabolism, hepatotoxicity, liver biology, and disease.
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