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TISSUE-SPECIFIC STEM CELLS

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

^aDepartment of Internal Medicine,
^bResearch Centre for Experimental Medicine (CeRMS), University of Torino, Torino, Italy;
^c Fresenius Medical Care Deutschland GmbH, Bad Homburg, Germany;
^dUniversity of Milano, Division of Liver Transplantation, Ospedale Maggiore Istituto di Ricovero e Cura a Carattere Scientifico, Milano, Italy

Key Words. Progenitor cells • Hepatocytes • Liver injury • Mesenchymal stem cells • Pluripotent differentiation

Correspondence: Giovanni Camussi, M.D., 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; e-mail: giovanni.camussi{at}unito.it

Received on February 27, 2006; accepted for publication on August 22, 2006.

First published online in STEM CELLS EXPRESS  August 31, 2006.


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, -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 -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.

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