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The biliary tree—a reservoir of multipotent stem cells

Nature Reviews Gastroenterology & Hepatology volume 9, pages 231–240 (2012)Cite this article

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Abstract

The biliary tree is composed of intrahepatic and extrahepatic bile ducts, lined by mature epithelial cells called cholangiocytes, and contains peribiliary glands deep within the duct walls. Branch points, such as the cystic duct, perihilar and periampullar regions, contain high numbers of these glands. Peribiliary glands contain multipotent stem cells, which self-replicate and can differentiate into hepatocytes, cholangiocytes or pancreatic islets, depending on the microenvironment. Similar cells—presumably committed progenitor cells—are found in the gallbladder (which lacks peribiliary glands). The stem and progenitor cell characteristics indicate a common embryological origin for the liver, biliary tree and pancreas, which has implications for regenerative medicine as well as the pathophysiology and oncogenesis of midgut organs. This Perspectives article describes a hypothetical model of cell lineages starting in the duodenum and extending to the liver and pancreas, and thought to contribute to ongoing organogenesis throughout life.

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Figure 1: Embryological development of the liver, pancreas and biliary tree is triggered by endodermal proliferation.
Figure 2: Peribiliary glands in the hepatopancreatic ampulla.
Figure 3: Stem cell niches in the intrahepatic and extrahepatic biliary tree.
Figure 4: Proposed maturational cell lineages in the biliary tree.

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Acknowledgements

We thank G. Mendel for providing the original artwork for Figures 1 and 3 in this article. We also thank Giacomo Lanzoni, Luca Inverardi and Juan Dominez-Bendala for help with proofreading the manuscript, particularly sections on pancreatic progenitors. V. Cardinale received a scholarship from Sapienza University of Rome and research funding for his studies at University of North Carolina, NC, USA. Authors' research at University of North Carolina has been supported by sponsorship agreements with Vesta Therapeutics, Vertex Pharmaceuticals, GigaCyte Biotech, a grant from the North Carolina Biotechnology Center and funds from the Lineberger Cancer Center. D. Alvaro, V. Cardinale, E. Gaudio and G. Carpino have received grants from Agenzia Regionale del Lazio per Trapianti e Patologie connesse and from FIRB (Fondo per gli Investimenti della Ricerca di Base (RBAP10Z7FS_001 and RBAP10Z7FS_004). E. Gaudio and D. Alvaro were supported by MIUR (Ministero dell'Istruzione, dell'Universite della Ricerca) grants PRIN#2007, prot.2007HPT7BA_001 and PRIN# 2009X84L84_002, and Federate Athenaeum funds from the University Sapienza of Rome.

Author information

Authors and Affiliations

  1. Division of Gastroenterology, Department of Medico–Surgical Sciences and Biotechnology, Fondazione Eleonora Lorillard Spencer Cenci, Polo Pontino, Corso della Repubblica 79, Latina, 04100, Italy

    Vincenzo Cardinale & Domenico Alvaro

  2. Department of Human Anatomy, Sapienza University of Rome, Via Borelli 50, Rome, 00161, Italy

    Eugenio Gaudio

  3. Department of Cell and Molecular Physiology, University of North Carolina School of Medicine, Chapel Hill, 27599, NC, USA

    Yunfang Wang & Lola M. Reid

  4. Department of Biomedical Engineering, University of North Carolina School of Medicine, Chapel Hill, 27599, NC, USA

    Gemma Mendel

  5. Department of Health Sciences, University of Rome, Foro Italico, Piazza L. De Bosis 6, Rome, 00135, Italy

    Guido Carpino

  6. Division of Research, Central Texas Veterans Health Care System, Scott & White and Texas A & M Health Science Center College of Medicine, Olin E. Teague Medical Center, 1901 South 1st Street, Building 205, 1R60, Temple, 76504, TX, USA

    Gianfranco Alpini

Authors
  1. Vincenzo Cardinale
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  2. Yunfang Wang
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  3. Guido Carpino
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  4. Gemma Mendel
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  5. Gianfranco Alpini
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  6. Eugenio Gaudio
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  7. Lola M. Reid
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  8. Domenico Alvaro
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Contributions

The equal first authors, V. Cardinale and Y. Wang contributed to researching information, discussions of content, writing and editing the manuscript. The equal senior authors (E. Gaudio, L. M. Reid and D. Alvaro) also participated in researching information, discussions of content, writing and editing this article. G. Carpino contributed to researching information, content discussions, editing and writing the article. G. Alpini wrote a section and edited the manuscript. G. Mendel contributed to editing the article before submission.

Corresponding author

Correspondence to Domenico Alvaro.

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The authors declare no competing financial interests.

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Cardinale, V., Wang, Y., Carpino, G. et al. The biliary tree—a reservoir of multipotent stem cells. Nat Rev Gastroenterol Hepatol 9, 231–240 (2012). https://doi.org/10.1038/nrgastro.2012.23

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