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Tomlinson, L, Hyndman, L, Firman, JW, Bentley, R, Kyffin, JA, Webb, SD, McGinty, S and Sharma, P (2019) In vitro Liver Zonation of Primary Rat Hepatocytes. Frontiers in Bioengineering and Biotechnology, 7 (17). ISSN 2296-4185
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Tomlinson et al. 2019.pdf - Published Version Available under License Creative Commons Attribution. Download (1MB) | Preview |
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: | Article |
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| Subjects: | R Medicine > RM Therapeutics. Pharmacology |
| Divisions: | Applied Mathematics (merged with Comp Sci 10 Aug 20) Pharmacy & Biomolecular Sciences |
| Publisher: | Frontiers Media |
| Date Deposited: | 19 Feb 2019 12:17 |
| Last Modified: | 04 Sep 2021 01:58 |
| DOI or ID number: | 10.3389/fbioe.2019.00017 |
| URI: | https://researchonline.ljmu.ac.uk/id/eprint/10184 |
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