title: Viability, function and morphological integrity of precision-cut liver slices during prolonged incubation: Effects of culture medium.
abstract: Precision-cut liver slices (PCLS) are an ex vivo model for metabolism and toxicity studies. However, data on the maintenance of the morphological integrity of the various cell types in the slices during prolonged incubation are lacking. Therefore, our aims were to characterize morphological and functional changes in rat PCLS during five days of incubation in a rich medium, RegeneMed®, and a standard medium, Williams' Medium E. Although cells of all types in the slices remain viable, profound changes in morphology were observed, which were more prominent in RegeneMed®. Slices underwent notable fibrosis, bile duct proliferation and fat deposition. Slice thickness increased, resulting in necrotic areas, while slice diameter decreased, possibly indicating cell migration. An increased proliferation of parenchymal and non-parenchymal cells (NPCs) was observed. Glycogen, albumin and Cyp3a1 were maintained albeit to a different level in two media. In conclusion, both hepatocytes and NPCs remain viable and functional, enabling five-day toxicity studies. Tissue remodeling and formation of a new capsule-like cell lining around the slices are evident after 3–4 days. The differences in effects between media emphasize the importance of media selection and of the recognition of morphological changes in PCLS, when interpreting results from toxicological or pharmacological studies.
authors.affiliation: Division of Pharmacokinetics, Toxicology and Targeting, Groningen Research Institute for Pharmacy, University of Groningen, Antonius Deusinglaan 1, 9713 AV Groningen, The Netherlands.
authors.forename: Viktoriia
authors.initials: V
authors.lastname: Starokozhko
authors.affiliation: Division of Pharmacokinetics, Toxicology and Targeting, Groningen Research Institute for Pharmacy, University of Groningen, Antonius Deusinglaan 1, 9713 AV Groningen, The Netherlands.
authors.forename: Getahun B
authors.initials: GB
authors.lastname: Abza
authors.affiliation: Division of Pharmacokinetics, Toxicology and Targeting, Groningen Research Institute for Pharmacy, University of Groningen, Antonius Deusinglaan 1, 9713 AV Groningen, The Netherlands.
authors.forename: Hedy C
authors.initials: HC
authors.lastname: Maessen
authors.affiliation: Division of Pharmacokinetics, Toxicology and Targeting, Groningen Research Institute for Pharmacy, University of Groningen, Antonius Deusinglaan 1, 9713 AV Groningen, The Netherlands.
authors.forename: Marjolijn T
authors.initials: MT
authors.lastname: Merema
authors.affiliation: TNO, Utrechtseweg 48, 3704 HE Zeist, The Netherlands.
authors.forename: Frieke
authors.initials: F
authors.lastname: Kuper
authors.affiliation: Division of Pharmacokinetics, Toxicology and Targeting, Groningen Research Institute for Pharmacy, University of Groningen, Antonius Deusinglaan 1, 9713 AV Groningen, The Netherlands. Electronic address: g.m.m.groothuis@rug.nl.
authors.forename: Geny M M
authors.initials: GM
authors.lastname: Groothuis
mesh_terms: D000255:Adenosine Triphosphate / Q000032:analysis; D000818:Animals; D049109:Cell Proliferation; D003470:Culture Media; D006706:Homeostasis; D066298:In Vitro Techniques; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D050356:Lipid Metabolism; D008099:Liver / Q000473:pathology / Q000502:physiology*; D008297:Male; D051381:Rats; D017208:Rats, Wistar
chemical_list: D003470:Culture Media; D000255:Adenosine Triphosphate; D007770:L-Lactate Dehydrogenase
keywords: Precision-cut liver slices; Prolonged incubation