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 - Publisher Copyright:
© 2017 The Author(s)
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 liver stem cells
KW - disease modeling
KW - feline hepatic lipidosis
KW - feline liver organoids
KW - hepatic steatosis
KW - species differences
UR - http://www.scopus.com/inward/record.url?scp=85016035787&partnerID=8YFLogxK
U2 - 10.1016/j.stemcr.2017.02.015
DO - 10.1016/j.stemcr.2017.02.015
M3 - Article
C2 - 28344000
AN - SCOPUS:85016035787
SN - 2213-6711
VL - 8
SP - 822
EP - 830
JO - Stem Cell Reports
JF - Stem Cell Reports
IS - 4
ER -