1. Long-Term Adult Feline Liver Organoid Cultures for Disease Modeling of Hepatic Steatosis
- Author
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Kruitwagen, Hedwig S., Oosterhoff, Loes A., Vernooij, Ingrid G W H, Schrall, Ingrid M., van Wolferen, Monique E., Bannink, Farah, Roesch, Camille, van Uden, Lisa, Molenaar, Martijn R., Helms, J. Bernd, Grinwis, Guy C.M., Verstegen, Monique M A, van der Laan, Luc J W, Huch, Meritxell, Geijsen, Niels, Vries, Robert R G, Clevers, Hans, Rothuizen, Jan, Schotanus, Baukje A., Penning, Louis C., Spee, Bart, dB&C FR-RMSC FR, dCSCA RMSC-1, dPB CR, dCSCA AVR, Onderzoek, Biochemisch laboratorium, LS Pathologie, Sub Biochemie Algemeen, Dep Biochemie en Celbiologie, LS Veterinaire biochemie, Veterinair Pathologisch Diagnostisch Cnt, PB AVM, Applied Veterinary Research, Dep Pathobiologie, Faculteit Diergeneeskunde, LS Interne geneeskunde, Surgery, Hubrecht Institute for Developmental Biology and Stem Cell Research, dB&C FR-RMSC FR, dCSCA RMSC-1, dPB CR, dCSCA AVR, Onderzoek, Biochemisch laboratorium, LS Pathologie, Sub Biochemie Algemeen, Dep Biochemie en Celbiologie, LS Veterinaire biochemie, Veterinair Pathologisch Diagnostisch Cnt, PB AVM, Applied Veterinary Research, Dep Pathobiologie, Faculteit Diergeneeskunde, LS Interne geneeskunde, Huch Ortega, Meritxell [0000-0002-1545-5265], and Apollo - University of Cambridge Repository
- Subjects
0301 basic medicine ,Male ,Pathology ,species differences ,Biochemistry ,Liver disease ,0302 clinical medicine ,Lipid droplet ,disease modeling ,Non-U.S. Gov't ,lcsh:QH301-705.5 ,lcsh:R5-920 ,Research Support, Non-U.S. Gov't ,hepatic steatosis ,Fatty liver ,Cell Differentiation ,3. Good health ,Organoids ,Adult Stem Cells ,Liver ,030220 oncology & carcinogenesis ,Female ,Stem cell ,lcsh:Medicine (General) ,Adult stem cell ,Feline hepatic lipidosis ,medicine.medical_specialty ,feline liver organoids ,Biology ,Research Support ,03 medical and health sciences ,Organ Culture Techniques ,Report ,Internal medicine ,Genetics ,medicine ,Organoid ,Journal Article ,Animals ,Animal ,Cell Biology ,medicine.disease ,Fatty Liver ,Disease Models, Animal ,adult liver stem cells ,030104 developmental biology ,Endocrinology ,lcsh:Biology (General) ,Disease Models ,Cats ,Hepatocytes ,feline hepatic lipidosis ,Steatosis ,Developmental Biology - Abstract
Summary 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., Highlights • Feline organoids can be cultured from fresh and frozen liver and from needle biopsy • A feline-specific liver culture medium allows organoid expansion up to 32 passages • When fed fatty acids, feline liver organoids store more lipids than human organoids • Feline liver organoids can be used to model hepatic steatosis, In this study Kruitwagen and colleagues establish and characterize a feline liver organoid culture, which has adult stem cell properties and can be differentiated toward hepatocyte-like cells. They propose liver organoids as a tool to model hepatic steatosis and show that feline liver organoids accumulate more lipids than human organoids when provided with excess fatty acids.
- Published
- 2017