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Organoids and Spheroids as Models for Studying Cholestatic Liver Injury and Cholangiocarcinoma
Author(s) -
Sato Keisaku,
Zhang Wenjun,
Safarikia Samira,
Isidan Abdulkadir,
Chen Angela M.,
Li Ping,
Francis Heather,
Kennedy Lindsey,
Baiocchi Leonardo,
Alvaro Domenico,
Glaser Shan,
Ekser Burcin,
Alpini Gianfranco
Publication year - 2021
Publication title -
hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.488
H-Index - 361
eISSN - 1527-3350
pISSN - 0270-9139
DOI - 10.1002/hep.31653
Subject(s) - organoid , hepatic stellate cell , cancer research , progenitor cell , biology , primary sclerosing cholangitis , induced pluripotent stem cell , cell , cell culture , cell type , microbiology and biotechnology , pathology , stem cell , medicine , embryonic stem cell , disease , biochemistry , genetics , gene
Cholangiopathies, such as primary sclerosing cholangitis, biliary atresia, and cholangiocarcinoma, have limited experimental models. Not only cholangiocytes but also other hepatic cells including hepatic stellate cells and macrophages are involved in the pathophysiology of cholangiopathies, and these hepatic cells orchestrate the coordinated response against diseased conditions. Classic two‐dimensional monolayer cell cultures do not resemble intercellular cell‐to‐cell interaction and communication; however, three‐dimensional cell culture systems, such as organoids and spheroids, can mimic cellular interaction and architecture between hepatic cells. Previous studies have demonstrated the generation of hepatic or biliary organoids/spheroids using various cell sources including pluripotent stem cells, hepatic progenitor cells, primary cells from liver biopsies, and immortalized cell lines. Gene manipulation, such as transfection and transduction can be performed in organoids, and established organoids have functional characteristics which can be suitable for drug screening. This review summarizes current methodologies for organoid/spheroid formation and a potential for three‐dimensional hepatic cell cultures as in vitro models of cholangiopathies.