Hepatic Progenitor Cells and Biliary Tree Stem Cells

  • Guido Carpino
  • Sergio MoriniEmail author
  • Simone Carotti
  • Eugenio Gaudio


In the adult human liver, hepatic stem/progenitor cells (HPCs) are facultative bipotential stem cells which reside in the canals of Hering and in bile ductules. HPCs have a unique phenotype and are capable to differentiate towards hepatocytes and cholangiocytes. The differentiation toward a more mature phenotype is characterized by the progressive acquisition of mature traits and the appearance of a progeny with an intermediate phenotype.

HPCs are surrounded by a specialized niche, composed of portal myofibroblasts, hepatic stellate cells, and resident macrophages. The niche furnishes key signals, such as Notch and Wnt pathways, and drives HPC response, including proliferation and differentiation toward a mature fate.

In normal condition, HPCs are quiescent since the physiological turnover of liver parenchyma is endured by the proliferation of hepatocytes and cholangiocytes. The activation of HPC compartment takes place in human diseases when proliferative capabilities of mature cells are exhausted or impaired. The hallmark of HPC activation is represented by the appearance of the ductular reaction, which correlates with the severity of liver damage and is associated with fibrogenesis.

Beside HPCs, large intrahepatic and extrahepatic bile ducts contain a population of stem/progenitor cells collectively named biliary tree stem/progenitor cells (BTSCs). BTSCs reside within peribiliary glands along the biliary tree, are activated in human primary sclerosing cholangitis, and participate in biliary strictures.

The isolation of HPCs and BTSCs from adult or fetal human organs is easy, requires minimal manipulation and no reprogramming. The use of these cells has been proposed for the regenerative medicine of the liver and pancreas.


Stem cell Liver regeneration Cholangiopathies WNT Notch Fibrosis 


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Copyright information

© Springer Nature Switzerland AG 2020

Authors and Affiliations

  • Guido Carpino
    • 1
  • Sergio Morini
    • 2
    Email author
  • Simone Carotti
    • 2
  • Eugenio Gaudio
    • 3
  1. 1.Department of Motor, Human and Health SciencesUniversity of Rome “Foro Italico”RomeItaly
  2. 2.Department of Medicine and SurgeryUniversity Campus Bio-Medico of RomeRomeItaly
  3. 3.Department of Anatomical, Histological, Locomotor and Legal Medicine SciencesSapienza UniversityRomeItaly

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