ArticleHepatology (Baltimore, Md.)2019
Peribiliary Glands Are Key in Regeneration of the Human Biliary Epithelium After Severe Bile Duct Injury.
Article in Hepatology (Baltimore, Md.), 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers, 1 of them a synthesis that pooled it.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
35 citing papers in PubMed, 1 synthesis or guideline pooled it, 64 citations in OpenAlex.
- Biliary Viability Assessment and Treatment Options of Biliary Injury During Normothermic Liver Perfusion-A Systematic Review.Transplant international : official journal of the European Society for Organ Transplantation · 2022Pooled it
- Enhanced Peribiliary Gland Detachment in Aged Donor Grafts After Rat Liver Transplantation.Transplantation direct · 2026Article
- What we can learn from hibernators and other adapted animals about organ transplantation: mechanisms of cold resistance and enhanced regeneration.Protein & cell · 2026Article
- Melatonin Alleviates Graft Biliary Fibrosis by Inhibiting VIMAdvanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Spectrum of Biliary and Nonbiliary Neoplasms Growing and Spreading Within the Lumen of the Bile Ducts.Cancers · 2026Review
- A Novel Bioabsorbable Covered Stent for Advancing Bile Duct Injury Management: A Preclinical Study in a Porcine Model (With Video).DEN open · 2026Article
- Hepatic Artery Infusion Pump Therapy for Intrahepatic Cholangiocarcinoma: Indications and Outcomes.Journal of gastrointestinal cancer · 2025Review
- 10 degree C static storage of porcine donation after circulatory death livers improves biliary viability and mitigates ischemia-reperfusion injury.American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons · 2025Article
- Consensus classification of biliary complications after liver transplantation: guidelines from the BileducTx meeting.The British journal of surgery · 2025Article
- Long-term machine perfusion of human split livers: a new model for regenerative and translational research.Nature communications · 2024Review
- Biliary fibrosis is an important but neglected pathological feature in hepatobiliary disorders: from molecular mechanisms to clinical implications.Medical review (2021) · 2024Review
- Biliary atresia.Nature reviews. Disease primers · 2024Review
- Extrahepatic Bile Duct Organoids as a Model to Study Ischemia/Reperfusion Injury During Liver Transplantation.Transplant international : official journal of the European Society for Organ Transplantation · 2024Article
- Cholangiocyte Organoids in Liver Transplantation; a Comprehensive Review.Transplant international : official journal of the European Society for Organ Transplantation · 2024Review
- Heterogeneous murine peribiliary glands orchestrate compartmentalized epithelial renewal.Developmental cell · 2023Article
- A fetal wound healing program after intrauterine bile duct injury may contribute to biliary atresia.Journal of hepatology · 2023Article
- Bile proteome reveals biliary regeneration during normothermic preservation of human donor livers.Nature communications · 2023Article
- Human precision-cut cystic duct and gallbladder slices: a novel method for studying cholangiopathies.Frontiers in pediatrics · 2023Article
- Pitfalls and promises of bile duct alternatives: A narrative review.World journal of gastroenterology · 2022Review
- Design by Nature: Emerging Applications of Native Liver Extracellular Matrix for Cholangiocyte Organoid-Based Regenerative Medicine.Bioengineering (Basel, Switzerland) · 2022Review
Corrections and comments
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Authors and funding
16 authors at 4 institutions in 3 countries.
Funding
Abstract
Peribiliary glands (PBG) are a source of stem/progenitor cells organized in a cellular network encircling large bile ducts. Severe cholangiopathy with loss of luminal biliary epithelium has been proposed to activate PBG, resulting in cell proliferation and differentiation to restore biliary epithelial integrity. However, formal evidence for this concept in human livers is lacking. We therefore developed an ex vivo model using precision-cut slices of extrahepatic human bile ducts obtained from discarded donor livers, providing an intact anatomical organization of cell structures, to study spatiotemporal differentiation and migration of PBG cells after severe biliary injury. Postischemic bile duct slices were incubated in oxygenated culture medium for up to a week. At baseline, severe tissue injury was evident with loss of luminal epithelial lining and mural stroma necrosis. In contrast, PBG remained relatively well preserved and different reactions of PBG were noted, including PBG dilatation, cell proliferation, and maturation. Proliferation of PBG cells increased after 24 hours of oxygenated incubation, reaching a peak after 72 hours. Proliferation of PBG cells was paralleled by a reduction in PBG apoptosis and differentiation from a primitive and pluripotent (homeobox protein Nanog+/ sex-determining region Y-box 9+) to a mature (cystic fibrosis transmembrane conductance regulator+/secretin receptor+) and activated phenotype (increased expression of hypoxia-inducible factor 1 alpha, glucose transporter 1, and vascular endothelial growth factor A). Migration of proliferating PBG cells in our ex vivo model was unorganized, but resulted in generation of epithelial monolayers at stromal surfaces. Conclusion: Human PBG contain biliary progenitor cells and are able to respond to bile duct epithelial loss with proliferation, differentiation, and maturation to restore epithelial integrity. The ex vivo spatiotemporal behavior of human PBG cells provides evidence for a pivotal role of PBG in biliary regeneration after severe injury.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.