Title
Viability, function and morphological integrity of precision-cut liver slices during prolonged incubation: Effects of culture medium
Author
Starokozhko, V.
Abza, G.B.
Maessen, H.C.
Merema, M.T.
Kuper, F.
Groothuis, G.M.M.
Publication year
2015
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. © 2015 Elsevier B.V.
Subject
Life
RAPID - Risk Analysis for Products in Development
EELS - Earth, Environmental and Life Sciences
Biomedical Innovation
Biology
Healthy Living
Precision-cut liver slices
Prolonged incubation
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DOI
https://doi.org/10.1016/j.tiv.2015.10.008
TNO identifier
533501
ISSN
0887-2333
Source
Toxicology in Vitro, 30 (1), 288-299
Document type
article