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Stem Cells International
Volume 2016, Article ID 3658013, 12 pages
Review Article

Stem/Progenitor Cell Niches Involved in Hepatic and Biliary Regeneration

1Department of Movement, Human and Health Sciences, Division of Health Sciences, University of Rome “Foro Italico”, Piazza Lauro De Bosis 6, 00135 Rome, Italy
2Department of Anatomical, Histological, Forensic Medicine and Orthopedics Sciences, Sapienza University of Rome, Via Borelli 50, 00161 Rome, Italy
3Eleonora Lorillard Spencer-Cenci Foundation, Piazzale Aldo Moro 5, 00185 Rome, Italy
4Department of Medico-Surgical Sciences and Biotechnologies, Sapienza University of Rome, Corso della Repubblica 79, 04100 Latina, LT, Italy
5Department of Cell Biology and Physiology, Chapel Hill, NC 27599, USA
6Program in Molecular Biology and Biotechnology, Chapel Hill, NC 27599, USA
7Lineberger Comprehensive Cancer Center, Chapel Hill, NC 27599, USA

Received 10 August 2015; Revised 16 November 2015; Accepted 23 November 2015

Academic Editor: Toru Hosoda

Copyright © 2016 Guido Carpino 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.


Niches containing stem/progenitor cells are present in different anatomical locations along the human biliary tree and within liver acini. The most primitive stem/progenitors, biliary tree stem/progenitor cells (BTSCs), reside within peribiliary glands located throughout large extrahepatic and intrahepatic bile ducts. BTSCs are multipotent and can differentiate towards hepatic and pancreatic cell fates. These niches’ matrix chemistry and other characteristics are undefined. Canals of Hering (bile ductules) are found periportally and contain hepatic stem/progenitor cells (HpSCs), participating in the renewal of small intrahepatic bile ducts and being precursors to hepatocytes and cholangiocytes. The niches also contain precursors to hepatic stellate cells and endothelia, macrophages, and have a matrix chemistry rich in hyaluronans, minimally sulfated proteoglycans, fetal collagens, and laminin. The microenvironment furnishes key signals driving HpSC activation and differentiation. Newly discovered third niches are pericentral within hepatic acini, contain Axin2+ unipotent hepatocytic progenitors linked on their lateral borders to endothelia forming the central vein, and contribute to normal turnover of mature hepatocytes. Their relationship to the other stem/progenitors is undefined. Stem/progenitor niches have important implications in regenerative medicine for the liver and biliary tree and in pathogenic processes leading to diseases of these tissues.