In vitro liver zonation of primary rat hepatocytes

Tomlinson, L., Hyndman, L., Firman, J. W., Bentley, R., Kyffin, J. A., Webb, S. D., McGinty, S. and Sharma, P. (2019) In vitro liver zonation of primary rat hepatocytes. Frontiers in Bioengineering and Biotechnology, 7, 17. (doi:10.3389/fbioe.2019.00017)

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Abstract

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 in vitro 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 in vitro 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:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Mcginty, Dr Sean and Hyndman, Miss Lauren
Authors: Tomlinson, L., Hyndman, L., Firman, J. W., Bentley, R., Kyffin, J. A., Webb, S. D., McGinty, S., and Sharma, P.
College/School:College of Science and Engineering > School of Engineering > Biomedical Engineering
Journal Name:Frontiers in Bioengineering and Biotechnology
Publisher:Frontiers
ISSN:2296-4185
ISSN (Online):2296-4185
Copyright Holders:Copyright © 2019 Tomlinson, Hyndman, Firman, Bentley, Kyffin, Webb, McGinty and Sharma
First Published:First published in Frontiers in Bioengineering and Biotechnology 7:17
Publisher Policy:Reproduced under a Creative Commons License

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
678901EPSRC DTG 2014Mary Beth KneafseyEngineering and Physical Sciences Research Council (EPSRC)EP/M506539/1R&I - RESEARCH STRATEGY & INNOVATION
701101EPSRC 2015 DTPMary Beth KneafseyEngineering and Physical Sciences Research Council (EPSRC)EP/M508056/1R&I - RESEARCH STRATEGY & INNOVATION