{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T12:17:07Z","timestamp":1785241027843,"version":"3.55.0"},"update-to":[{"DOI":"10.12688\/f1000research.142014.1","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2024,4,8]],"date-time":"2024-04-08T00:00:00Z","timestamp":1712534400000}}],"reference-count":27,"publisher":"F1000 Research Ltd","license":[{"start":{"date-parts":[[2024,4,8]],"date-time":"2024-04-08T00:00:00Z","timestamp":1712534400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100019533","name":"Moderna","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100019533","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["f1000research.com"],"crossmark-restriction":false},"short-container-title":["F1000Res"],"abstract":"<ns3:p>\n                    Background In academic research and the pharmaceutical industry,\n                    <ns3:italic>in vitro<\/ns3:italic>\n                    cell lines and\n                    <ns3:italic>in vivo<\/ns3:italic>\n                    animal models are considered as gold standards in modelling diseases and assessing therapeutic efficacy. However, both models have intrinsic limitations, whilst the use of precision-cut tissue slices can bridge the gap between these mainstream models. Precision-cut tissue slices combine the advantage of high reproducibility, studying all cell sub-types whilst preserving the tissue matrix and extracellular architecture, thereby closely mimicking a mini-organ. This approach can be used to replicate the biological phenotype of liver monogenic diseases using mouse models. Methods Here, we describe an optimised and easy-to-implement protocol for the culture of sections from mouse livers, enabling its use as a reliable\n                    <ns3:italic>ex-vivo<\/ns3:italic>\n                    model to assess the therapeutic screening of inherited metabolic diseases Results We show that precision-cut liver sections can be a reliable model for recapitulating the biological phenotype of inherited metabolic diseases, exemplified by common urea cycle defects such as citrullinemia type 1 and argininosuccinic aciduria, caused by argininosuccinic synthase (ASS1) and argininosuccinic lyase (ASL) deficiencies respectively. Conclusions Therapeutic response to gene therapy such as messenger RNA replacement delivered via lipid nanoparticles can be monitored, demonstrating that precision-cut liver sections can be used as a preclinical screening tool to assess therapeutic response and toxicity in monogenic liver diseases.\n                  <\/ns3:p>","DOI":"10.12688\/f1000research.142014.2","type":"journal-article","created":{"date-parts":[[2024,4,8]],"date-time":"2024-04-08T05:05:16Z","timestamp":1712552716000},"page":"1580","update-policy":"https:\/\/doi.org\/10.12688\/f1000research.crossmark-policy","source":"Crossref","is-referenced-by-count":5,"title":["Ex vivo precision-cut liver slices model disease phenotype and monitor therapeutic response for liver monogenic diseases"],"prefix":"10.12688","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5450-8801","authenticated-orcid":false,"given":"Dany","family":"Perocheau","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3271-5273","authenticated-orcid":false,"given":"Sonam","family":"Gurung","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Loukia","family":"Touramanidou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claire","family":"Duff","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Garima","family":"Sharma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Neil","family":"Sebire","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1333-5400","authenticated-orcid":false,"given":"Patrick F","family":"Finn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alex","family":"Cavedon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Summar","family":"Siddiqui","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisa","family":"Rice","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paolo G.V.","family":"Martini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Frassetto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julien","family":"Baruteau","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"2560","published-online":{"date-parts":[[2024,4,8]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"639-648","DOI":"10.1007\/s11427-015-4865-9","article-title":"The role of the microenvironment on the fate of adult stem cells.","volume":"58","author":"L Dong","year":"2015","journal-title":"Sci. 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Microbiol."},{"key":"ref7","doi-asserted-by":"publisher","first-page":"pdb.prot094011","DOI":"10.1101\/pdb.prot094011","article-title":"Cutting Thick Sections Using a Vibratome.","volume":"2017","author":"A Iulianella","year":"2017","journal-title":"Cold Spring Harb. Protoc."},{"key":"ref8","doi-asserted-by":"publisher","DOI":"10.3791\/60992","article-title":"Murine Precision-Cut Liver Slices as an ex vivo Model of Liver Biology.","author":"M Pearen","year":"2020","journal-title":"J. Vis. 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Sci."},{"key":"ref24","doi-asserted-by":"publisher","first-page":"1403-1411","DOI":"10.1002\/lt.20510","article-title":"Oxygenation during hypothermic rat liver preservation: an in vitro slice study to demonstrate beneficial or toxic oxygenation effects.","volume":"11","author":"N t Hart","year":"2005","journal-title":"Liver Transpl."},{"key":"ref25","doi-asserted-by":"publisher","first-page":"1513-1524","DOI":"10.1016\/j.tiv.2013.03.007","article-title":"Effect of oxygen concentration and selected protocol factors on viability and gene expression of mouse liver slices.","volume":"27","author":"E Szalowska","year":"2013","journal-title":"Toxicol. In Vitro."},{"key":"ref26","doi-asserted-by":"publisher","first-page":"1141-1153","DOI":"10.3748\/wjg.v18.i11.1141","article-title":"Genetically modified mouse models for the study of nonalcoholic fatty liver disease.","volume":"18","author":"P Nagarajan","year":"2012","journal-title":"World J. 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Best wishes Dany Perocheau and co authors","URL":"https:\/\/f1000research.com\/articles\/12-1580\/v2#referee-comment-11329","order":1,"name":"referee-comment-11329","label":"Referee Comment","group":{"name":"article-reports","label":"Article Reports"}},{"value":"10.5256\/f1000research.164319.r264017, Vicente Rubio, Instituto de Biomedicina de Valencia (IBV-CSIC), Valencia, Select One, 46010, 13 Apr 2024, version 2, indexed","URL":"https:\/\/f1000research.com\/articles\/12-1580\/v2#referee-response-264017","order":2,"name":"referee-response-264017","label":"Referee Report","group":{"name":"article-reports","label":"Article Reports"}},{"value":"This work was supported by funding from the United Kingdom Medical Research Council Clinician Scientist Fellowship MR\/T008024\/1 (JB) and funding from Moderna.","order":3,"name":"grant-information","label":"Grant Information"},{"value":"This is an open access article distributed under the terms of the Creative Commons Attribution Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.","order":0,"name":"copyright-info","label":"Copyright"}]}}