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利用脂肪基质或干细胞衍生类器官在人类中模拟酒精相关性肝病。

Modeling alcohol-associated liver disease in humans using adipose stromal or stem cell-derived organoids.

机构信息

Department of Cell Biology, School of Basic Medical Science, Capital Medical University, Beijing 100069, China.

Beijing Friendship Hospital, Capital Medical University, Beijing, China.

出版信息

Cell Rep Methods. 2024 May 20;4(5):100778. doi: 10.1016/j.crmeth.2024.100778. Epub 2024 May 14.

DOI:10.1016/j.crmeth.2024.100778
PMID:38749443
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11133832/
Abstract

Alcohol-associated liver disease (ALD) is a prevalent liver disease, yet research is hampered by the lack of suitable and reliable human ALD models. Herein, we generated human adipose stromal/stem cell (hASC)-derived hepatocellular organoids (hAHOs) and hASC-derived liver organoids (hALOs) in a three-dimensional system using hASC-derived hepatocyte-like cells and endodermal progenitor cells, respectively. The hAHOs were composed of major hepatocytes and cholangiocytes. The hALOs contained hepatocytes and nonparenchymal cells and possessed a more mature liver function than hAHOs. Upon ethanol treatment, both steatosis and inflammation were present in hAHOs and hALOs. The incubation of hALOs with ethanol resulted in increases in the levels of oxidative stress, the endoplasmic reticulum protein thioredoxin domain-containing protein 5 (TXNDC5), the alcohol-metabolizing enzymes ADH1B and ALDH1B1, and extracellular matrix accumulation, similar to those of liver tissues from patients with ALD. These results present a useful approach for understanding the pathogenesis of ALD in humans, thus facilitating the discovery of effective treatments.

摘要

酒精相关性肝病（ALD）是一种常见的肝脏疾病，但由于缺乏合适和可靠的人类 ALD 模型，研究受到了阻碍。在此，我们使用源自人脂肪基质/干细胞（hASC）的肝细胞样细胞和内胚层祖细胞，在三维系统中分别生成了源自人 ASC 的肝细胞类器官（hAHO）和人 ASC 衍生的肝类器官（hALO）。hAHO 由主要的肝细胞和胆管细胞组成。hALO 含有肝细胞和非实质细胞，其肝脏功能比 hAHO 更成熟。在乙醇处理后，hAHO 和 hALO 均出现脂肪变性和炎症。hALO 与乙醇孵育会导致氧化应激水平、内质网蛋白硫氧还蛋白结构域蛋白 5（TXNDC5）、酒精代谢酶 ADH1B 和 ALDH1B1 以及细胞外基质积累增加，类似于 ALD 患者的肝组织。这些结果提供了一种有用的方法来了解人类 ALD 的发病机制，从而促进有效治疗方法的发现。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/06c6/11133832/4e123bc0740a/gr7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/06c6/11133832/a9c650f87b94/fx1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/06c6/11133832/db595ef14dd7/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/06c6/11133832/5ff6f294de4d/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/06c6/11133832/271c6bc68e6b/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/06c6/11133832/3feeb7a662b2/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/06c6/11133832/5d96605a3da1/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/06c6/11133832/943007d7a276/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/06c6/11133832/4e123bc0740a/gr7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/06c6/11133832/a9c650f87b94/fx1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/06c6/11133832/db595ef14dd7/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/06c6/11133832/5ff6f294de4d/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/06c6/11133832/271c6bc68e6b/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/06c6/11133832/3feeb7a662b2/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/06c6/11133832/5d96605a3da1/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/06c6/11133832/943007d7a276/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/06c6/11133832/4e123bc0740a/gr7.jpg

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3
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