<i>In vitro</i> Liver Zonation of Primary Rat Hepatocytes

Tomlinson, Lauren, Hyndman, Lauren, Firman, James W, Bentley, Robert, Kyffin, Jonathan A, Webb, Steven D, McGinty, Sean and Sharma, Parveen ORCID: 0000-0002-5534-2417
(2019) <i>In vitro</i> Liver Zonation of Primary Rat Hepatocytes. FRONTIERS IN BIOENGINEERING AND BIOTECHNOLOGY, 7. 17-.

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The ability of the liver to simultaneously carry out multiple functions is dependent on the metabolic heterogeneity of hepatocytes spatially located within a liver lobule spanning from the portal triad to the central vein. This complex zonal architecture of the liver, however, makes accurate <i>in vitro</i> modeling a challenge and often standard culture systems assume a homogenous model which may lead to inaccurate translatability of results. Here, we use a combination of mathematical modeling and experimental data to demonstrate a readily constructible <i>in vitro</i> flow system capable of liver zonation in primary rat hepatocytes. We show the differential expression of zonation markers, enhanced functionality when compared to standard static cultures and zone-specific metabolism and cell damage in the presence of paracetamol, a known zone-specific toxin. This type of advanced system provides a more in-depth and essential understanding of liver physiology and pathophysiology as well as the accurate evaluation of pharmacological interventions at a zone-specific level.

Item Type: Article
Uncontrolled Keywords: liver zonation, mathematical modeling, flow system, drug-induced liver injury, in vitro model
Depositing User: Symplectic Admin
Date Deposited: 19 Feb 2019 10:35
Last Modified: 08 Oct 2023 21:13
DOI: 10.3389/fbioe.2019.00017
Open Access URL: https://doi.org/10.3389/fbioe.2019.00017
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URI: https://livrepository.liverpool.ac.uk/id/eprint/3033087