{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T15:37:26Z","timestamp":1791819446104,"version":"4.3.4"},"reference-count":27,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2019,2,18]],"date-time":"2019-02-18T00:00:00Z","timestamp":1550448000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000836","name":"University of Liverpool","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000836","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000849","name":"National Centre for the Replacement, Refinement and Reduction of Animals in Research","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000849","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000266","name":"Engineering and Physical Sciences Research Council","doi-asserted-by":"publisher","award":["EP\/M506539\/1"],"award-info":[{"award-number":["EP\/M506539\/1"]}],"id":[{"id":"10.13039\/501100000266","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000266","name":"Engineering and Physical Sciences Research Council","doi-asserted-by":"publisher","award":["EPM508056\/1"],"award-info":[{"award-number":["EPM508056\/1"]}],"id":[{"id":"10.13039\/501100000266","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Bioeng. Biotechnol."],"DOI":"10.3389\/fbioe.2019.00017","type":"journal-article","created":{"date-parts":[[2019,2,18]],"date-time":"2019-02-18T04:14:23Z","timestamp":1550463263000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":36,"title":["In vitro Liver Zonation of Primary Rat Hepatocytes"],"prefix":"10.3389","volume":"7","author":[{"given":"Lauren","family":"Tomlinson","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lauren","family":"Hyndman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James W.","family":"Firman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Bentley","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan A.","family":"Kyffin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven D.","family":"Webb","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sean","family":"McGinty","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Parveen","family":"Sharma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2019,2,18]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"253","DOI":"10.1002\/bit.10569","article-title":"Formation of steady-state oxygen gradients in vitro: application to liver zonation","volume":"82","author":"Allen","year":"2003","journal-title":"Biotechnol. Bioeng."},{"key":"B2","doi-asserted-by":"publisher","first-page":"760","DOI":"10.1038\/nbt.2989","article-title":"Microfluidic organs-on-chips","volume":"32","author":"Bhatia","year":"2014","journal-title":"Nat. Biotechnol."},{"key":"B3","doi-asserted-by":"publisher","first-page":"463","DOI":"10.1038\/ncb3349","article-title":"Orchestrating Wnt signalling for metabolic liver zonation","volume":"18","author":"Birchmeier","year":"2016","journal-title":"Nat. Cell Biol."},{"key":"B4","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1007\/978-1-4419-7107-4_2","article-title":"Liver zonation","volume-title":"Molecular Pathology of Liver Diseases","author":"Colnot","year":"2011"},{"key":"B5","doi-asserted-by":"publisher","first-page":"1159","DOI":"10.1517\/17425250903160664","article-title":"Liver tissue engineering in the evaluation of drug safety","volume":"5","author":"Dash","year":"2009","journal-title":"Expert Opin. Drug Metab. Toxicol."},{"key":"B6","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1177\/2397847317726351","article-title":"Organs-on-a-chip: a new paradigm for toxicological assessment and preclinical drug development","volume":"1","author":"David","year":"2017","journal-title":"Toxicol. Res. Appl."},{"key":"B7","doi-asserted-by":"publisher","first-page":"1053","DOI":"10.1039\/C6TX00101G","article-title":"Characterization of a functional C3A liver spheroid model","author":"Gaskell","year":"2016","journal-title":"Toxicol. Res."},{"key":"B8","doi-asserted-by":"publisher","first-page":"218","DOI":"10.1016\/j.bios.2014.07.029","article-title":"Advantages and challenges of microfluidic cell culture in polydimethylsiloxane devices","volume":"63","author":"Halldorsson","year":"2015","journal-title":"Biosens. Bioelectron."},{"key":"B9","doi-asserted-by":"publisher","first-page":"12741","DOI":"10.1073\/pnas.220176997","article-title":"Increased resistance to acetaminophen hepatotoxicity in mice lacking glutathione S-transferase Pi","volume":"97","author":"Henderson","year":"2000","journal-title":"Proc. Nat. Acad. Sci. U.S.A."},{"key":"B10","doi-asserted-by":"publisher","first-page":"2135","DOI":"10.1038\/nprot.2013.137","article-title":"Microfabrication of human organs-on-chips","volume":"8","author":"Huh","year":"2013","journal-title":"Nat. Protoc."},{"key":"B11","doi-asserted-by":"publisher","first-page":"8951","DOI":"10.1038\/s41598-018-27179-6","article-title":"Metabolic patterning on a chip: towards in vitro liver zonation of primary rat and human hepatocytes","volume":"8","author":"Kang","year":"2018","journal-title":"Sci. Rep."},{"key":"B12","doi-asserted-by":"publisher","first-page":"622","DOI":"10.1016\/j.redox.2017.01.012","article-title":"Metabolic zonation of the liver: the oxygen gradient revisited","volume":"11","author":"Kietzmann","year":"2017","journal-title":"Redox Biol."},{"key":"B13","doi-asserted-by":"publisher","first-page":"pdb.prot095497","DOI":"10.1101\/pdb.prot095497","article-title":"Analysis of cell viability by the lactate dehydrogenase assay","volume":"2018","author":"Kumar","year":"2018","journal-title":"Cold Spring Harbor Protocols"},{"key":"B14","doi-asserted-by":"publisher","first-page":"1936","DOI":"10.1021\/acs.chemrestox.6b00150","article-title":"Novel 3D culture systems for studies of human liver function and assessments of the hepatotoxicity of drugs and drug candidates","volume":"29","author":"Lauschke","year":"2016","journal-title":"Chem. Res. Toxicol."},{"key":"B15","doi-asserted-by":"publisher","first-page":"1743","DOI":"10.1002\/hep.28780","article-title":"Massive rearrangements of cellular MicroRNA signatures are key drivers of hepatocyte dedifferentiation","volume":"64","author":"Lauschkek","year":"2016","journal-title":"Hepatology"},{"key":"B16","doi-asserted-by":"publisher","first-page":"2","DOI":"10.1007\/bf03160941","article-title":"Acetaminophen-induced nephrotoxicity: pathophysiology, clinical manifestations, and management","volume":"4","author":"Mazer","year":"2008","journal-title":"J. Med. Toxicol."},{"key":"B17","doi-asserted-by":"publisher","first-page":"127","DOI":"10.1002\/bit.22671","article-title":"A low shear stress modular bioreactor for connected cell culture under high flow rates","volume":"106","author":"Mazzei","year":"2010","journal-title":"Biotechnol. Bioeng."},{"key":"B18","doi-asserted-by":"publisher","first-page":"26868","DOI":"10.1038\/srep26868","article-title":"A microfabricated platform for generating physiologically-relevant hepatocyte zonation","volume":"6","author":"McCarty","year":"2016","journal-title":"Sci. Rep."},{"key":"B19","doi-asserted-by":"publisher","first-page":"792","DOI":"10.1046\/j.0014-2956.2001.02687.x","article-title":"Implications of the simultaneous occurrence of hepatic glycolysis from glucose and gluconeogenesis from glycerol","volume":"269","author":"Phillips","year":"2002","journal-title":"Eur. J. Biochem."},{"key":"B20","doi-asserted-by":"publisher","first-page":"2065","DOI":"10.1002\/hep.23937","article-title":"Drug-induced acute liver failure: results of a U.S. multicenter, prospective study","volume":"52","author":"Reuben","year":"2010","journal-title":"Hepatology"},{"key":"B21","doi-asserted-by":"crossref","first-page":"138","DOI":"10.1007\/978-1-4614-3055-1_9","article-title":"Engineering quasi-vivo\u00aein vitro organ models","volume-title":"New Technologies for Toxicity Testing","author":"Sbrana","year":"2012"},{"key":"B22","doi-asserted-by":"publisher","first-page":"e363","DOI":"10.3389\/fphys.2015.00363","article-title":"Drug-induced liver toxicity and prevention by herbal antioxidants: an overview","volume":"6","author":"Singh","year":"2016","journal-title":"Front. Physiol."},{"key":"B23","doi-asserted-by":"publisher","first-page":"e26908","DOI":"10.1371\/journal.pone.0026908","article-title":"A simple protocol for using a LDH-based cytotoxicity assay to assess the effects of death and growth inhibition at the same time","volume":"6","author":"Smith","year":"2011","journal-title":"PLoS ONE"},{"key":"B24","doi-asserted-by":"publisher","first-page":"554","DOI":"10.1002\/biot.201000326","article-title":"Modular bioreactor for primary human hepatocyte culture: medium flow stimulates expression and activity of detoxification genes","volume":"6","author":"Vinci","year":"2011","journal-title":"Biotechnol. J."},{"key":"B25","doi-asserted-by":"publisher","first-page":"40","DOI":"10.1039\/c2tx20031g","article-title":"Novel in vitro and mathematical models for the prediction of chemical toxicity","volume":"2","author":"Williams","year":"2013","journal-title":"Toxicol. Res."},{"key":"B26","doi-asserted-by":"publisher","first-page":"563","DOI":"10.1002\/hep.24712","article-title":"Mature hepatocytes exhibit unexpected plasticity by direct dedifferentiation into liver progenitor cells in culture","volume":"55","author":"Yixin","year":"2012","journal-title":"Hepatology"},{"key":"B27","doi-asserted-by":"publisher","first-page":"11544","DOI":"10.1038\/srep11544","article-title":"Synthesis, characterization and apoptotic activity of quinazolinone Schiff base derivatives toward MCF-7 cells via intrinsic and extrinsic apoptosis pathways","volume":"5","author":"Zahedifard","year":"2015","journal-title":"Sci. Rep."}],"container-title":["Frontiers in Bioengineering and Biotechnology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/article\/10.3389\/fbioe.2019.00017\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2019,2,18]],"date-time":"2019-02-18T04:14:25Z","timestamp":1550463265000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/article\/10.3389\/fbioe.2019.00017\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,2,18]]},"references-count":27,"alternative-id":["10.3389\/fbioe.2019.00017"],"URL":"https:\/\/doi.org\/10.3389\/fbioe.2019.00017","relation":{},"ISSN":["2296-4185"],"issn-type":[{"value":"2296-4185","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,2,18]]},"article-number":"17"}}