Modelling fatty liver disease with mouse liver-derived multicellular spheroids.

Autor:	van Os EA; Liver Cell Biology Research Group, Vrije Universiteit Brussel, Laarbeeklaan 103, 1090, Brussels, Belgium., Cools L; Liver Cell Biology Research Group, Vrije Universiteit Brussel, Laarbeeklaan 103, 1090, Brussels, Belgium., Eysackers N; Liver Cell Biology Research Group, Vrije Universiteit Brussel, Laarbeeklaan 103, 1090, Brussels, Belgium., Szafranska K; Vascular Biology Research Group, Department of Medical Biology, University of Tromsø (UiT) - the Arctic University of Norway, Tromsø, Norway., Smout A; Liver Cell Biology Research Group, Vrije Universiteit Brussel, Laarbeeklaan 103, 1090, Brussels, Belgium., Verhulst S; Liver Cell Biology Research Group, Vrije Universiteit Brussel, Laarbeeklaan 103, 1090, Brussels, Belgium., Reynaert H; Liver Cell Biology Research Group, Vrije Universiteit Brussel, Laarbeeklaan 103, 1090, Brussels, Belgium., McCourt P; Vascular Biology Research Group, Department of Medical Biology, University of Tromsø (UiT) - the Arctic University of Norway, Tromsø, Norway., Mannaerts I; Liver Cell Biology Research Group, Vrije Universiteit Brussel, Laarbeeklaan 103, 1090, Brussels, Belgium., van Grunsven LA; Liver Cell Biology Research Group, Vrije Universiteit Brussel, Laarbeeklaan 103, 1090, Brussels, Belgium. Electronic address: leo.van.grunsven@vub.be.
Jazyk:	angličtina
Zdroj:	Biomaterials [Biomaterials] 2022 Nov; Vol. 290, pp. 121817. Date of Electronic Publication: 2022 Sep 28.
DOI:	10.1016/j.biomaterials.2022.121817
Abstrakt:	Chronic liver disease can lead to liver fibrosis and ultimately cirrhosis, which is a significant health burden and a major cause of death worldwide. Reliable in vitro models are lacking and thus mono-cultures of cell lines are still used to study liver disease and evaluate candidate anti-fibrotic drugs. We established functional multicellular liver spheroid (MCLS) cultures using primary mouse hepatocytes, hepatic stellate cells, liver sinusoidal endothelial cells and Kupffer cells. Cell-aggregation and spheroid formation was enhanced with 96-well U-bottom plates generating over ±700 spheroids from one mouse. Extensive characterization showed that MCLS cultures contain functional hepatocytes, quiescent stellate cells, fenestrated sinusoidal endothelium and responsive Kupffer cells that can be maintained for 17 days. MCLS cultures display a fibrotic response upon chronic exposure to acetaminophen, and present steatosis and fibrosis when challenged with free fatty acid and lipopolysaccharides, reminiscent of non-alcoholic fatty liver disease (NAFLD) stages. Treatment of MCLS cultures with potential anti-NAFLD drugs such as Elafibranor, Lanifibranor, Pioglitazone and Obeticholic acid shows that all can inhibit steatosis, but only Elafibranor and especially Lanifibranor inhibit fibrosis. Therefore, primary mouse MCLS cultures can be used to model acute and chronic liver disease and are suitable for the assessment of anti-NAFLD drugs. Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)
Databáze:	MEDLINE
Externí odkaz:	Full Text from ScienceDirect