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This study explores the use of precision-cut liver slices (PCLS) as an ex vivo model to evaluate new therapies. Researchers tested how different oxygen levels affect viability, tissue integrity, and inflammatory response in PCLS from healthy and fibrotic rats. Fibrotic PCLS maintained their pathological gene signature under 40% oxygen and responded to inflammatory stimuli, indicating preserved functionality. Exposure to high oxygen levels increased oxidative stress and pro-inflammatory gene expression. Cirrhotic PCLS showed early signs of reduced viability and the upregulation of fibrosis-related genes including Col1\u03b12, Col3\u03b11, \u03b1SMA, Timp1, Timp2, Mmp2, Pdgfr\u03b2, Nos2, Cox2, and Il6. Lipopolysaccharide (LPS) exposure induced the marked overexpression of Nos2 and Il1\u03b2 mRNA and confirmed the model\u2019s responsiveness to external injury. Fibrotic PCLS retained fibrogenic activity for at least 48 h. Additionally, the adenoviral delivery of a dominant-negative soluble PDGFR\u03b2 effectively blocked fibrotic signaling. Human fibrotic PCLS also remained viable for 72 h and showed an increased mRNA expression of fibrosis markers such as COL1A1, \u03b1SMA, and MMP2. These results highlight the potential of PCLS as a promising platform for future therapeutic testing, pending further validation with functional interventions.<\/jats:p>","DOI":"10.3390\/ijms26167780","type":"journal-article","created":{"date-parts":[[2025,8,13]],"date-time":"2025-08-13T07:45:31Z","timestamp":1755071131000},"page":"7780","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Precision-Cut Liver Slices: A Valuable Preclinical Tool for Translational Research in Liver Fibrosis"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1944-8337","authenticated-orcid":false,"given":"Meritxell","family":"Perram\u00f3n","sequence":"first","affiliation":[{"name":"Biochemistry and Molecular Genetics Service, Hospital Cl\u00ednic of Barcelona, Institut d\u2019Investigacions Biom\u00e8diques August Pi i Sunyer (IDIBAPS), 08036 Barcelona, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Hep\u00e1ticas y Digestivas (CIBERehd), ISCIII, 28029 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Manuel","family":"Mac\u00edas-Herranz","sequence":"additional","affiliation":[{"name":"Biochemistry and Molecular Genetics Service, Hospital Cl\u00ednic of Barcelona, Institut d\u2019Investigacions Biom\u00e8diques August Pi i Sunyer (IDIBAPS), 08036 Barcelona, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Hep\u00e1ticas y Digestivas (CIBERehd), ISCIII, 28029 Madrid, Spain"},{"name":"Department of Biomedicine, University of Barcelona, 08036 Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Roc\u00edo","family":"Garc\u00eda-P\u00e9rez","sequence":"additional","affiliation":[{"name":"Hepatopancreatobiliary Surgery & Transplantation, General & Digestive Surgery Service, Digestive & Metabolic Disease Institute (ICMDM), Hospital Cl\u00ednic of Barcelona, 08036 Barcelona, Spain"},{"name":"Department of Medicine, University of Barcelona, 08036 Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9376-0214","authenticated-orcid":false,"given":"Wladimiro","family":"Jim\u00e9nez","sequence":"additional","affiliation":[{"name":"Biochemistry and Molecular Genetics Service, Hospital Cl\u00ednic of Barcelona, Institut d\u2019Investigacions Biom\u00e8diques August Pi i Sunyer (IDIBAPS), 08036 Barcelona, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Hep\u00e1ticas y Digestivas (CIBERehd), ISCIII, 28029 Madrid, Spain"},{"name":"Department of Biomedicine, University of Barcelona, 08036 Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7776-3300","authenticated-orcid":false,"given":"Guillermo","family":"Fern\u00e1ndez-Varo","sequence":"additional","affiliation":[{"name":"Biochemistry and Molecular Genetics Service, Hospital Cl\u00ednic of Barcelona, Institut d\u2019Investigacions Biom\u00e8diques August Pi i Sunyer (IDIBAPS), 08036 Barcelona, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Hep\u00e1ticas y Digestivas (CIBERehd), ISCIII, 28029 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,8,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"718","DOI":"10.1016\/j.jhep.2018.05.011","article-title":"Burden of liver disease in Europe: Epidemiology and analysis of risk factors to identify prevention policies","volume":"69","author":"Pimpin","year":"2018","journal-title":"J. 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