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长期成年猫类肝类器官培养用于肝脂肪变性的疾病建模。

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

机构信息

Department of Clinical Sciences of Companion Animals, Faculty of Veterinary Medicine, Utrecht University, 3584 CM Utrecht, the Netherlands.

Department of Clinical Sciences of Companion Animals, Faculty of Veterinary Medicine, Utrecht University, 3584 CM Utrecht, the Netherlands.

出版信息

Stem Cell Reports. 2017 Apr 11;8(4):822-830. doi: 10.1016/j.stemcr.2017.02.015. Epub 2017 Mar 23.

DOI:10.1016/j.stemcr.2017.02.015
PMID:28344000
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5390114/
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.

摘要

肝脂肪变性是一种高发的肝脏疾病，但由于缺乏易于处理的细胞和动物模型，相关研究受到了阻碍。脂肪变性也会发生在猫身上，可导致严重的肝衰竭。先前的研究表明，类器官在遗传疾病建模方面具有潜力。为了研究使用类器官来模拟脂肪变性的可能性，我们建立了一种具有成年肝干细胞特征和向肝样细胞分化潜力的长期猫肝类器官培养体系。接下来，我们用脂肪酸处理来自鼠、人、犬和猫肝的类器官。我们观察到所有类器官中都有脂质积累，有趣的是，猫肝类器官比人源类器官积累了更多的脂滴。最后，我们证明了干扰β-氧化对猫肝类器官脂质积累的影响。总之，我们成功培养了猫肝类器官，并发现其具有脂质积累的倾向，这使得它们成为肝脂肪变性研究中的一个有趣模型。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d518/5390114/1b4053801eac/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d518/5390114/5fae60159f96/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d518/5390114/58444ee1501b/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d518/5390114/fc24943d786d/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d518/5390114/1b4053801eac/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d518/5390114/5fae60159f96/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d518/5390114/58444ee1501b/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d518/5390114/fc24943d786d/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d518/5390114/1b4053801eac/gr4.jpg

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