PDF(Pubmed)
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）是一种常见的肝病，然而，缺乏合适和可靠的人类ALD模型阻碍了研究。在这里，我们使用hASC衍生的肝细胞样细胞和内胚层祖细胞在三维系统中产生了人脂肪基质/干细胞（hASC）衍生的肝细胞类器官（hAHOs）和hASC衍生的肝脏类器官（hALOs）。分别。hAHO由主要肝细胞和胆管细胞组成。hALO含有肝细胞和非实质细胞，并且比hAHO具有更成熟的肝功能。在乙醇处理后，脂肪变性和炎症均存在于hAHO和hALO中。hALOs与乙醇的孵育导致氧化应激水平的增加，含有硫氧还蛋白结构域的内质网蛋白5（TXNDC5），酒精代谢酶ADH1B和ALDH1B1和细胞外基质积累，与ALD患者的肝组织相似。这些结果为理解人类ALD的发病机理提供了有用的方法，从而有利于发现有效的治疗方法。
