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J Hepatol. 2006 Jun;44(6):1115-24. Epub 2005 Nov 7.

The expression of mesenchymal, neural and haematopoietic stem cell markers in adult hepatocytes proliferating in vitro.

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  • 1Department of General Surgery, Georg-August University Goettingen, Germany.

Abstract

BACKGROUND/AIMS:

Cultured adult hepatocytes may be stimulated into clonal expansion. We raise the question whether adult hepatocytes proliferating in vitro recapitulate the early process of hepatic development.

METHODS:

A non-enzymatic method was used to isolate hepatocytes free of contamination with non-parenchymal cells. Hepatocytes were stimulated into proliferation in the presence of mitogens and conditioned media from non-parenchymal cell and hepatocyte culture supernatants. Immunofluorescence methods and PCR analysis were used to demonstrate immunophenotypical characteristics and gene expression profiles similar to those of progenitor cells.

RESULTS:

Rapid growth occurred during the first 7 days of culture. Cells continued to express hepatic markers (phosphoenolpyruvate carboxykinase, cytokeratin 18, transferrin and dipeptidylpeptidase IV), but the gap junction protein connexin 32 was down-regulated. In the early stage of proliferation, cells started to express biliary and extrahepatic progenitor markers (cytokeratin 19, CD49b, CD49f, nestin, vimentin, Thy1 and c-kit), followed by cytokeratin 7, connexin 43, and neural cell adhesion molecule. Co-expression of the epithelial liver progenitor marker alpha-foetoprotein with either nestin (neural marker) or Thy1 (mesenchymal marker) was also demonstrated.

CONCLUSIONS:

Mature hepatocytes reveal their potential to regain a spectrum of progenitor markers from different germ layers, suggesting enormous plasticity and differentiation potential of adult liver cells.

[PubMed - indexed for MEDLINE]
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