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

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

N1 - Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

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 -