Isolation and Characterization of a Stem Cell Population from Adult Human Liver

Authors

  • Maria Beatriz Herrera,

    1. Department of Internal Medicine, University of Torino, Torino, Italy
    2. Research Centre for Experimental Medicine (CeRMS), University of Torino, Torino, Italy
    Search for more papers by this author
  • Stefania Bruno,

    1. Department of Internal Medicine, University of Torino, Torino, Italy
    2. Research Centre for Experimental Medicine (CeRMS), University of Torino, Torino, Italy
    Search for more papers by this author
  • Stefano Buttiglieri,

    1. Department of Internal Medicine, University of Torino, Torino, Italy
    2. Research Centre for Experimental Medicine (CeRMS), University of Torino, Torino, Italy
    Search for more papers by this author
  • Ciro Tetta,

    1. Fresenius Medical Care Deutschland GmbH, Bad Homburg, Germany
    Search for more papers by this author
  • Stefano Gatti,

    1. University of Milano, Division of Liver Transplantation, Ospedale Maggiore Istituto di Ricovero e Cura a Carattere Scientifico, Milano, Italy
    Search for more papers by this author
  • Maria Chiara Deregibus,

    1. Department of Internal Medicine, University of Torino, Torino, Italy
    2. Research Centre for Experimental Medicine (CeRMS), University of Torino, Torino, Italy
    Search for more papers by this author
  • Benedetta Bussolati,

    1. Department of Internal Medicine, University of Torino, Torino, Italy
    2. Research Centre for Experimental Medicine (CeRMS), University of Torino, Torino, Italy
    Search for more papers by this author
  • Giovanni Camussi M.D.

    Corresponding author
    1. Department of Internal Medicine, University of Torino, Torino, Italy
    2. Research Centre for Experimental Medicine (CeRMS), University of Torino, Torino, Italy
    • Cattedra di Nefrologia, Dipartimento di Medicina Interna Ospedale Maggiore S. Giovanni Battista, Corso Dogliotti 14, 10126, Torino, Italy. Telephone: +39-011-6336708; Fax: +39-011-6631184
    Search for more papers by this author

Abstract

Several studies suggested the presence of stem cells in the adult normal human liver; however, a population with stem cell properties has not yet been isolated. The purpose of the present study was to identify and characterize progenitor cells in normal adult human liver. By stringent conditions of liver cell cultures, we isolated and characterized a population of human liver stem cells (HLSCs). HLSCs expressed the mesenchymal stem cell markers CD29, CD73, CD44, and CD90 but not the hematopoietic stem cell markers CD34, CD45, CD117, and CD133. HLSCs were also positive for vimentin and nestin, a stem cell marker. The absence of staining for cytokeratin-19, CD117, and CD34 indicated that HLSCs were not oval stem cells. In addition, HLSCs expressed albumin, α-fetoprotein, and in a small percentage of cells, cytokeratin-8 and cytokeratin-18, indicating a partial commitment to hepatic cells. HLSCs differentiated in mature hepatocytes when cultured in the presence of hepatocyte growth factor and fibroblast growth factor 4, as indicated by the expression of functional cytochrome P450, albumin, and urea production. Under this condition, HLSCs downregulated α-fetoprotein and expressed cytokeratin-8 and cytokeratin-18. HLSCs were also able to undergo osteogenic and endothelial differentiation when cultured in the appropriated differentiation media, but they did not undergo lipogenic differentiation. Moreover, HLSCs differentiated in insulin-producing islet-like structures. In vivo, HLSCs contributed to regeneration of the liver parenchyma in severe-combined immunodeficient mice. In conclusion, we here identified a pluripotent progenitor population in adult human liver that could provide a basis for cell therapy strategies.

Ancillary