ArticlePediatric surgery international2020
A novel model of injured liver ductal organoids to investigate cholangiocyte apoptosis with relevance to biliary atresia.
Article in Pediatric surgery international, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 23 citations in OpenAlex.
- Single-cell RNA Sequencing Analysis Reveals That Targeting PLG-PLGRKT Signaling-mediated Pro-fibrotic Scar-associated Macrophages Ameliorates Liver Fibrosis in Biliary Atresia.Journal of clinical and translational hepatology · 2026Article
- Reporting Completeness of Biliary Atresia Organoid Studies: A Scoping Review and Structured Audit.Journal of clinical and translational hepatology · 2026Review
- Anti-fibrotic effect of human amniotic fluid stem cells in biliary epithelial-mesenchymal transition of liver ductal organoid.Stem cells translational medicine · 2025Article
- MtDNA 3243 A>G mutation and recurrent cholangitis after Kasai procedure in biliary atresia: a case report.Translational pediatrics · 2025Article
- Vitamin D3/VDR alleviates double-stranded RNA virus -induced biliary epithelial cell damage by inhibiting autophagy.BMC gastroenterology · 2025Article
- Advances in liver organoids: replicating hepatic complexity for toxicity assessment and disease modeling.Stem cell research & therapy · 2025Review
- Research on biliary atresia and epigenetic factors from the perspective of transcriptomics: identification of key genes and experimental validation.Frontiers in pediatrics · 2025Article
- Hepatobiliary organoid research: the progress and applications.Frontiers in pharmacology · 2025Review
- Innate immunity of bile and cholangiocytes in primary biliary cholangitis.Frontiers in immunology · 2025Review
- Autoimmune diseases refractory to corticosteroids and immunosuppressants.Frontiers in immunology · 2024Review
- Development of liver inflammatory injury in biliary atresia: from basic to clinical research.Pediatric surgery international · 2023Review
- Cholangiokines: undervalued modulators in the hepatic microenvironment.Frontiers in immunology · 2023Review
- Serum TGF-Computational and mathematical methods in medicine · 2022Article
- Visualizing transfer of microbial biomolecules by outer membrane vesicles in microbe-host-communication in vivo.Journal of extracellular vesicles · 2021Article
- Biliary Epithelial Senescence in Liver Disease: There Will Be SASP.Frontiers in molecular biosciences · 2021Review
- Animal and Organoid Models of Liver Fibrosis.Frontiers in physiology · 2021Review
- The Potential Application of Magnetic Nanoparticles for Liver Fibrosis Theranostics.Frontiers in chemistry · 2021Review
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purposeThe fibrogenic process in cholangiopathic diseases such as biliary atresia (BA) involves bile duct injury and apoptosis of cholangiocytes, which leads to the progression of liver fibrosis into liver cirrhosis and can result in end-staged liver disease. Recent advances in the development of organoids or mini-organ structures have allowed us to create an ex vivo injury model of the bile duct that mimics bile duct injury in BA. The aim of this experimental study was to develop a novel model of injured intrahepatic cholangiocytes as this can be relevant to BA. Our new model is important for studying the pathophysiological response of bile ducts to injury and the role of cholangiocytes in initiating the fibrogenic cascade. In addition, it has the potential to be used as a tool for developing new treatment strategies for BA.
methodsLiver ductal organoids were generated from the liver of healthy neonatal mouse pups. Intrahepatic bile duct fragments were isolated and cultured in Matrigel dome. Injury was induced in the organoids by administration of acetaminophen in culture medium. The organoids were then evaluated for fibrogenic cytokines expression, cell apoptosis marker and cell proliferation marker.
resultsOrganoids generated from intrahepatic bile duct fragments organized themselves into single-layer epithelial spheroids with lumen on the inside mimicking in vivo bile ducts. After 24-h exposure to acetaminophen, cholangiocytes in the organoids responded to the injury by increasing expression of fibrogenic cytokines, transforming growth factor beta-1 (TGF-β1) and platelet-derived growth factor-BB (PDGF-BB). This fibrogenic response of injured organoids was associated with increased cholangiocyte apoptosis and decreased cholangiocyte proliferation.
conclusionTo our knowledge this is the first description of cholangiocyte injury in the organoids derived from intrahepatic bile ducts. Our injury model demonstrated that cholangiocyte apoptosis and its fibrogenic response may play a role in initiation of the fibrogenic process in cholangiopathic diseases such as BA. These findings are important for the development of novel therapy to reduce cholangiocyte apoptosis and to halt the early fibrogenic cascade in liver fibrogenesis. This novel injury model can prove very valuable for future research in biliary atresia.
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