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

Research output: Contribution to journal/periodicalArticleScientificpeer-review

72 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)822-830
Number of pages9
JournalStem Cell Reports
Volume8
Issue number4
DOIs
Publication statusPublished - 11 Apr 2017

Keywords

  • Adult Stem Cells
  • Animals
  • Cats
  • Cell Differentiation
  • Disease Models, Animal
  • Fatty Liver
  • Female
  • Hepatocytes
  • Liver
  • Male
  • Organ Culture Techniques
  • Organoids
  • Journal Article
  • Research Support, Non-U.S. Gov't

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