Generation of Organoids from Mouse Extrahepatic Bile Ducts

Shiota, Junya; Zaki, Nureen H. Mohamad; Merchant, Juanita L.; Samuelson, Linda C.; Razumilava, Nataliya

doi:10.3791/59544-v

Cited by 3 publications

(2 citation statements)

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“…Nakagawa et al, (43) Shiota et al (44) Mouse gallbladder • IHC and mRNA abundance of progenitor, epithelial, hepatocyte, and biliary markers CRISPR-Cas9-assisted mutagenesis, carcinogenesis, and regenerative potential Lugli et al, (47) Scanu et al, (64) Erlangga et al (65) Abbreviations: ALP, alkaline phosphatase; FXR, Farnesoid X-activated receptor; IHC, immunohistochemistry.…”

Section: Genetic Models Of Biliary Cancer and Disease Modelingmentioning

confidence: 99%

“…(40) Mouse studies also identified a clonogenic subpopulation of suppression of tumorigenicity 14-positive cholangiocytes that can proliferate and produce longterm biliary organoids. (42) Cholangiocyte-like cell organoids could also be generated from dissociated mouse EHBDs, (43,44) expressing markers of mature cholangiocytes (Krt19, aquaporin 1) and progenitor cells (Lgr5), which have been used to study normal cholangiocyte biology (44) and EHBD cancer. (43) A major advance was reported in 2018 when Soroka et al (38) showed that human organoid cultures could be generated from cholangiogram-obtained bile, thereby overcoming the limitation of invasive access to human biliary tissue.…”

Section: Genetic Models Of Biliary Cancer and Disease Modelingmentioning

confidence: 99%

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Hepatobiliary Organoids and Their Applications for Studies of Liver Health and Disease: Are We There Yet?

2021

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Organoid culture systems have emerged as a frontier technology in liver and biliary research. These three‐dimensional (3D) cell cultures derived from pluripotent and adult hepatobiliary cells model organ structure and function. Building on gastrointestinal organoid establishment, hepatobiliary organoid cultures were generated from mouse leucine‐rich repeat–containing G‐protein–coupled receptor 5–positive liver progenitor cells. Subsequently, 3D hepatobiliary organoid cultures were developed from hepatocytes and cholangiocytes to model human and animal hepatobiliary health and disease. Hepatocyte organoids have been used to study Alagille syndrome, fatty liver disease, Wilson disease, hepatitis B viral infection, and cystic fibrosis. Cholangiocyte organoids have been established to study normal cholangiocyte biology and primary sclerosing cholangitis and to test organoid potential to form bile ducts and gallbladder tissue in vitro. Hepatobiliary cancer organoids, termed tumoroids, have been established from frozen and fresh human tissues and used as a drug‐testing platform and for biobanking of cancer samples. CRISPR‐based gene modifications and organoid exposure to infectious agents have permitted the generation of organoid models of carcinogenesis. This review summarizes currently available adult cell–derived hepatobiliary organoid models and their applications. Challenges faced by this young technology will be discussed, including the cellular immaturity of organoid‐derived hepatocytes, co‐culture development to better model complex tissue structure, the imperfection of extracellular matrices, and the absence of standardized protocols and model validation.

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