Long-Term Adult Feline Liver Organoid Cultures for Disease Modeling of Hepatic Steatosis

Hedwig S Kruitwagen, Loes A Oosterhoff, Ingrid G W H Vernooij, Ingrid M Schrall, Monique E van Wolferen, Farah Bannink, Camille Roesch, Lisa van Uden, Martijn R Molenaar, J Bernd Helms, Guy C M Grinwis, Monique M A Verstegen, Luc J W van der Laan, Meritxell Huch, Niels Geijsen, Robert G Vries, Hans Clevers, Jan Rothuizen, Baukje A Schotanus, Louis C PenningBart Spee

Onderzoeksoutput: Bijdrage aan wetenschappelijk tijdschrift/periodieke uitgaveArtikelWetenschappelijkpeer review

Samenvatting

Hepatic steatosis is a highly prevalent liver disease, yet research is hampered by the lack of tractable cellular and animal models. Steatosis also occurs in cats, where it can cause severe hepatic failure. Previous studies demonstrate the potential of liver organoids for modeling genetic diseases. To examine the possibility of using organoids to model steatosis, we established a long-term feline liver organoid culture with adult liver stem cell characteristics and differentiation potential toward hepatocyte-like cells. Next, organoids from mouse, human, dog, and cat liver were provided with fatty acids. Lipid accumulation was observed in all organoids and interestingly, feline liver organoids accumulated more lipid droplets than human organoids. Finally, we demonstrate effects of interference with β-oxidation on lipid accumulation in feline liver organoids. In conclusion, feline liver organoids can be successfully cultured and display a predisposition for lipid accumulation, making them an interesting model in hepatic steatosis research.

Originele taal-2Engels
Pagina's (van-tot)822-830
Aantal pagina's9
TijdschriftStem Cell Reports
Volume8
Nummer van het tijdschrift4
DOI's
StatusGepubliceerd - 11 apr 2017

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