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 Penning; Bart Spee

doi:10.1016/j.stemcr.2017.02.015

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

Hubrecht Institute

Research output: Contribution to journal/periodical › Article › Scientific › peer-review

85 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 language	English
Pages (from-to)	822-830
Number of pages	9
Journal	Stem Cell Reports
Volume	8
Issue number	4
DOIs	https://doi.org/10.1016/j.stemcr.2017.02.015
Publication status	Published - 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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10.1016/j.stemcr.2017.02.015

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Kruitwagen, H. S., Oosterhoff, L. A., Vernooij, I. G. W. H., Schrall, I. M., van Wolferen, M. E., Bannink, F., Roesch, C., van Uden, L., Molenaar, M. R., Helms, J. B., Grinwis, G. C. M., Verstegen, M. M. A., van der Laan, L. J. W., Huch, M., Geijsen, N., Vries, R. G., Clevers, H., Rothuizen, J., Schotanus, B. A., ... Spee, B. (2017). Long-Term Adult Feline Liver Organoid Cultures for Disease Modeling of Hepatic Steatosis. Stem Cell Reports, 8(4), 822-830. https://doi.org/10.1016/j.stemcr.2017.02.015

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title = "Long-Term Adult Feline Liver Organoid Cultures for Disease Modeling of Hepatic Steatosis",

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.",

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",

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

year = "2017",

month = apr,

day = "11",

doi = "10.1016/j.stemcr.2017.02.015",

language = "English",

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journal = "Stem Cell Reports",

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Kruitwagen, HS, Oosterhoff, LA, Vernooij, IGWH, Schrall, IM, van Wolferen, ME, Bannink, F, Roesch, C, van Uden, L, Molenaar, MR, Helms, JB, Grinwis, GCM, Verstegen, MMA, van der Laan, LJW, Huch, M, Geijsen, N, Vries, RG, Clevers, H, Rothuizen, J, Schotanus, BA, Penning, LC & Spee, B 2017, 'Long-Term Adult Feline Liver Organoid Cultures for Disease Modeling of Hepatic Steatosis', Stem Cell Reports, vol. 8, no. 4, pp. 822-830. https://doi.org/10.1016/j.stemcr.2017.02.015

TY - JOUR

T1 - Long-Term Adult Feline Liver Organoid Cultures for Disease Modeling of Hepatic Steatosis

AU - Kruitwagen, Hedwig S

AU - Oosterhoff, Loes A

AU - Vernooij, Ingrid G W H

AU - Schrall, Ingrid M

AU - van Wolferen, Monique E

AU - Bannink, Farah

AU - Roesch, Camille

AU - van Uden, Lisa

AU - Molenaar, Martijn R

AU - Helms, J Bernd

AU - Grinwis, Guy C M

AU - Verstegen, Monique M A

AU - van der Laan, Luc J W

AU - Huch, Meritxell

AU - Geijsen, Niels

AU - Vries, Robert G

AU - Clevers, Hans

AU - Rothuizen, Jan

AU - Schotanus, Baukje A

AU - Penning, Louis C

AU - Spee, Bart

PY - 2017/4/11

Y1 - 2017/4/11

N2 - 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.

AB - 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.

KW - Adult Stem Cells

KW - Animals

KW - Cats

KW - Cell Differentiation

KW - Disease Models, Animal

KW - Fatty Liver

KW - Female

KW - Hepatocytes

KW - Liver

KW - Male

KW - Organ Culture Techniques

KW - Organoids

KW - Journal Article

KW - Research Support, Non-U.S. Gov't

U2 - 10.1016/j.stemcr.2017.02.015

DO - 10.1016/j.stemcr.2017.02.015

M3 - Article

C2 - 28344000

SN - 2213-6711

VL - 8

SP - 822

EP - 830

JO - Stem Cell Reports

JF - Stem Cell Reports

IS - 4

ER -

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

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Keywords

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