In vitro Liver Zonation of Primary Rat Hepatocytes
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 vitr...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2019-02-01
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| Series: | Frontiers in Bioengineering and Biotechnology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/article/10.3389/fbioe.2019.00017/full |
| _version_ | 1818283921318608896 |
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| author | Lauren Tomlinson Lauren Hyndman James W. Firman James W. Firman Robert Bentley Jonathan A. Kyffin Steven D. Webb Steven D. Webb Sean McGinty Parveen Sharma |
| author_facet | Lauren Tomlinson Lauren Hyndman James W. Firman James W. Firman Robert Bentley Jonathan A. Kyffin Steven D. Webb Steven D. Webb Sean McGinty Parveen Sharma |
| author_sort | Lauren Tomlinson |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-13T00:44:35Z |
| format | Article |
| id | doaj.art-e09f9906a319479d8aec40549ac751c6 |
| institution | Directory Open Access Journal |
| issn | 2296-4185 |
| language | English |
| last_indexed | 2024-12-13T00:44:35Z |
| publishDate | 2019-02-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Bioengineering and Biotechnology |
| spelling | doaj.art-e09f9906a319479d8aec40549ac751c62022-12-22T00:05:04ZengFrontiers Media S.A.Frontiers in Bioengineering and Biotechnology2296-41852019-02-01710.3389/fbioe.2019.00017421882In vitro Liver Zonation of Primary Rat HepatocytesLauren Tomlinson0Lauren Hyndman1James W. Firman2James W. Firman3Robert Bentley4Jonathan A. Kyffin5Steven D. Webb6Steven D. Webb7Sean McGinty8Parveen Sharma9MRC Centre for Drug Safety Science, Department of Clinical and Molecular Pharmacology, University of Liverpool, Liverpool, United KingdomDivision of Biomedical Engineering, University of Glasgow, Glasgow, United KingdomMRC Centre for Drug Safety Science, Department of Clinical and Molecular Pharmacology, University of Liverpool, Liverpool, United KingdomDepartment of Pharmacy and Biomolecular Science, Liverpool John Moores University, Liverpool, United KingdomMRC Centre for Drug Safety Science, Department of Clinical and Molecular Pharmacology, University of Liverpool, Liverpool, United KingdomDepartment of Applied Mathematics, Liverpool John Moores University, Liverpool, United KingdomDepartment of Applied Mathematics, Liverpool John Moores University, Liverpool, United KingdomEPSRC Liverpool Centre for Mathematics in Healthcare, Department of Mathematical Sciences, University of Liverpool, Liverpool, United KingdomDivision of Biomedical Engineering, University of Glasgow, Glasgow, United KingdomMRC Centre for Drug Safety Science, Department of Clinical and Molecular Pharmacology, University of Liverpool, Liverpool, United KingdomThe 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.https://www.frontiersin.org/article/10.3389/fbioe.2019.00017/fullliver zonationmathematical modelingflow systemdrug-induced liver injuryin vitro model |
| spellingShingle | Lauren Tomlinson Lauren Hyndman James W. Firman James W. Firman Robert Bentley Jonathan A. Kyffin Steven D. Webb Steven D. Webb Sean McGinty Parveen Sharma In vitro Liver Zonation of Primary Rat Hepatocytes Frontiers in Bioengineering and Biotechnology liver zonation mathematical modeling flow system drug-induced liver injury in vitro model |
| title | In vitro Liver Zonation of Primary Rat Hepatocytes |
| title_full | In vitro Liver Zonation of Primary Rat Hepatocytes |
| title_fullStr | In vitro Liver Zonation of Primary Rat Hepatocytes |
| title_full_unstemmed | In vitro Liver Zonation of Primary Rat Hepatocytes |
| title_short | In vitro Liver Zonation of Primary Rat Hepatocytes |
| title_sort | in vitro liver zonation of primary rat hepatocytes |
| topic | liver zonation mathematical modeling flow system drug-induced liver injury in vitro model |
| url | https://www.frontiersin.org/article/10.3389/fbioe.2019.00017/full |
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