ISOLATION AND CHARACTERIZATION OF A STEM CELL POPULATION FROM ADULT HUMAN LIVER

¹ Department of Internal Medicine, University of Torino, Torino, Italy; Research Centre for Experimental Medicine (CeRMS), University of Torino, Torino, Italy
² Fresenius Medical Care Deutschland GmbH, Bad Homburg, Germany
³ University of Milano, Division of Liver Transplantation, Ospedale Maggiore IRCCS, Milano, Italy

^* To whom correspondence should be addressed. E-mail: giovanni.camussi{at}unito.it.

	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 (HLSC). HLSC expressed the mesenchymal stem cell markers CD29, CD73, CD44, CD90 but not the hematopoietic stem cell markers CD34, CD45, CD117 and CD133. HLSC were also positive for vimentin and nestin, a stem cell marker. The absence of staining for cytokeratin-19, CD117 and CD34 indicated that HLSC were not oval stem cells. In addition HLSC expressed albumin, -fetoprotein, and in a small percentage of cells cytokeratin-8 and cytokeratin-18 indicating a partial commitment to hepatic cells. HLSC 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. In this condition, HLSC down-regulated -fetoprotein and expressed cytokeratin-8 and cytokeratin-18. HLSC were also able to undergo osteogenic and endothelial differentiation when cultured in the appropriated differentiation media, but they did not undergo lipogenic differentiation. Moreover, HLSC differentiated in insulin-producing islet-like structures. In vivo, HLSC contributed to regeneration of the liver parenchyma in SCID 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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