ABSTRACT Owing to the lack of suitable models, disease modeling and drug development and toxicity assessment for primary sclerosing cholangitis (PSC) face significant challenges. In recent years, major advances have been made in PSC disease modeling, rapid drug screening, and toxicity evaluation due to the development of organoid technology, gene editing, and bioengineering techniques. This review not only summarizes the pathogenesis and characteristics of PSC animal models but also details the latest progress in organoid models and engineered organoids. First, we introduce in vivo mouse models of PSC, which replicate bile stasis, biliary aging, and peribiliary inflammation, including gene‐edited mice (multidrug resistance‐related protein‐2 Mdr2 ) and chemical models (3,5‐Diethoxycarbonyl‐1,4‐dihydroxyphenyl‐2,4,6‐collidine DDC‐fed). We subsequently discuss the characteristics and research progress of primary cholangiocytes, cell lines, cholangiocyte organoids, and engineered organoids. In summary, we emphasize the role of novel in vitro and in vivo models in simulating PSC disease progression, developing new drugs, and conducting toxicity assessments.
Yao et al. (2026) studied this question.