Long-Term Adult Feline Liver Organoid Cultures for Disease Modeling of Hepatic Steatosis.
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.
Department of Clinical Sciences of Companion Animals, Faculty of Veterinary Medicine, Utrecht University, 3584 CM Utrecht, the Netherlands. Electronic address: h.s.kruitwagen@uu.nl.
Hedwig S
HS
Kruitwagen
Department of Clinical Sciences of Companion Animals, Faculty of Veterinary Medicine, Utrecht University, 3584 CM Utrecht, the Netherlands.
Loes A
LA
Oosterhoff
Department of Clinical Sciences of Companion Animals, Faculty of Veterinary Medicine, Utrecht University, 3584 CM Utrecht, the Netherlands.
Ingrid G W H
IGWH
Vernooij
Department of Clinical Sciences of Companion Animals, Faculty of Veterinary Medicine, Utrecht University, 3584 CM Utrecht, the Netherlands.
Ingrid M
IM
Schrall
Department of Clinical Sciences of Companion Animals, Faculty of Veterinary Medicine, Utrecht University, 3584 CM Utrecht, the Netherlands.
Monique E
ME
van Wolferen
Department of Clinical Sciences of Companion Animals, Faculty of Veterinary Medicine, Utrecht University, 3584 CM Utrecht, the Netherlands.
Farah
F
Bannink
Department of Clinical Sciences of Companion Animals, Faculty of Veterinary Medicine, Utrecht University, 3584 CM Utrecht, the Netherlands.
Camille
C
Roesch
Department of Clinical Sciences of Companion Animals, Faculty of Veterinary Medicine, Utrecht University, 3584 CM Utrecht, the Netherlands.
Lisa
L
van Uden
Department of Biochemistry and Cell Biology, Faculty of Veterinary Medicine & Institute of Biomembranes, Utrecht University, 3584 CM Utrecht, the Netherlands.
Martijn R
MR
Molenaar
Department of Biochemistry and Cell Biology, Faculty of Veterinary Medicine & Institute of Biomembranes, Utrecht University, 3584 CM Utrecht, the Netherlands.
J Bernd
JB
Helms
Department of Pathobiology, Faculty of Veterinary Medicine, Utrecht University, 3584 CL Utrecht, the Netherlands.
Guy C M
GCM
Grinwis
Department of Surgery, Erasmus MC-University Medical Center, 3000 CA Rotterdam, the Netherlands.
Monique M A
MMA
Verstegen
Department of Surgery, Erasmus MC-University Medical Center, 3000 CA Rotterdam, the Netherlands.
Luc J W
LJW
van der Laan
Hubrecht Institute, University Medical Centre, Utrecht University, 3584 CT Utrecht, the Netherlands.
Meritxell
M
Huch
Department of Clinical Sciences of Companion Animals, Faculty of Veterinary Medicine, Utrecht University, 3584 CM Utrecht, the Netherlands; Hubrecht Institute, University Medical Centre, Utrecht University, 3584 CT Utrecht, the Netherlands.
Niels
N
Geijsen
Hubrecht Institute, University Medical Centre, Utrecht University, 3584 CT Utrecht, the Netherlands.
Robert G
RG
Vries
Hubrecht Institute, University Medical Centre, Utrecht University, 3584 CT Utrecht, the Netherlands.
Hans
H
Clevers
Department of Clinical Sciences of Companion Animals, Faculty of Veterinary Medicine, Utrecht University, 3584 CM Utrecht, the Netherlands.
Jan
J
Rothuizen
Department of Clinical Sciences of Companion Animals, Faculty of Veterinary Medicine, Utrecht University, 3584 CM Utrecht, the Netherlands.
Baukje A
BA
Schotanus
Department of Clinical Sciences of Companion Animals, Faculty of Veterinary Medicine, Utrecht University, 3584 CM Utrecht, the Netherlands.
Louis C
LC
Penning
Department of Clinical Sciences of Companion Animals, Faculty of Veterinary Medicine, Utrecht University, 3584 CM Utrecht, the Netherlands.
Bart
B
Spee
D053687:Adult Stem Cells / Q000166:cytology / Q000473:pathology*; D000818:Animals; D002415:Cats; D002454:Cell Differentiation; D004195:Disease Models, Animal; D005234:Fatty Liver / Q000473:pathology*; D005260:Female; D022781:Hepatocytes / Q000166:cytology / Q000473:pathology; D008099:Liver / Q000166:cytology / Q000473:pathology*; D008297:Male; D009924:Organ Culture Techniques / Q000379:methods*; D009940:Organoids / Q000166:cytology / Q000473:pathology*
adult liver stem cells; disease modeling; feline hepatic lipidosis; feline liver organoids; hepatic steatosis; species differences