Table of Contents
Advances in Hepatology
Volume 2014, Article ID 794953, 10 pages
Review Article

Cholangiocarcinomas: New Insights from the Discovery of Stem Cell Niches in Peribiliary Glands of the Biliary Tree

1Department of Medico-Surgical Sciences and Biotechnologies, Polo Pontino, Sapienza University of Rome, Rome, Italy
2Department of Anatomical, Histological, Forensic Medicine and Orthopedics Sciences, Sapienza University of Rome, Rome, Italy
3Department of Movement, Human and Health Sciences, Division of Health Sciences, University of Rome “Foro Italico”, Rome, Italy
4Department of Cell Biology and Physiology, Program in Molecular Biology and Biotechnology, University of North Carolina School of Medicine, Chapel Hill, NC 27599, USA
5Eleonora Lorillard Spencer-Cenci Foundation, Rome, Italy

Received 11 December 2013; Revised 23 February 2014; Accepted 17 March 2014; Published 24 April 2014

Academic Editor: Mustapha Najimi

Copyright © 2014 Vincenzo Cardinale et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Peribiliary glands (PBGs) are located in the large intrahepatic and extrahepatic bile ducts. Although they were described many years ago, their functions have been elucidated only in the last couple of years when our group demonstrated that PBGs are niches of multipotent stem/progenitor cells of endodermal origin. These cells express genes of multipotency and can be rapidly differentiated in vitro into hepatocytes, cholangiocytes, and endocrine pancreatic cells. PBGs share common features, in terms of stem/progenitor cell niches, with pancreatic duct glands and colon crypts, glandular structures representing in the adult life the endodermal remnants of fetal life. PBG stem/progenitor cells participate in the renewal of surface biliary epithelium and are active players in chronic pathologies of the biliary tree as well as in cholangiocarcinomas (CCA). Specifically, a large amount of recent evidence indicates that the pure mucin-CCA originates from PBGs; this could explain the similarities with pancreatic ductal adenocarcinoma and colorectal cancer, which also originate from transformed gland cells. In this paper, we summarized our recent findings concerning structure and functions of PBGs with the implications for liver pathophysiology and, specifically, for cancers of the biliary tree.