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

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

Cell reports methods (2024-05-16)
Guoyun Bi, Xuan Zhang, Weihong Li, Xin Lu, Xu He, Yaqiong Li, Rixing Bai, Haiyan Zhang
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.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Monoclonal Anti-GSTA2, (N-terminal) antibody produced in mouse, clone 3D4, purified immunoglobulin, buffered aqueous solution
Sigma-Aldrich
Monoclonal Anti-Albumin antibody produced in mouse, clone HSA-11, ascites fluid
Sigma-Aldrich
N-Acetyl-L-cysteine, Sigma Grade, ≥99% (TLC), powder