Analysis in activation of hepatic stem/progenitor cells and development of application to hepatic tissue engineering

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Oval cells and small hepatocytes(SHs) are known as hepatic stem and progenitor cells, and Thy1 and CD44 are used as a marker, respectively. Although oval cells are believed to differentiate into mature hepatocytes(MHs) through SHs, the details of their differentiation process are not well understood. In the present experiment we used Thy1^+ oval and CD44^+cells isolated from D-galactosamine-treated rat livers. (1) EGF, basic FGF, or HGF could trigger the hepatic differentiation of sorted Thy1^+ cells to form epithelial cell colonies. (2) Thy1^+oval and CD44^+cells are able to differentiate into hepatocytes, the degree of hepatic maturation of the induced hepatocytes may not be equal to that of normal resident ones. (3) Thy1^+, CD44^+cells and MHs were transplanted into livers treated with retrorsine following partial hepatectomy. Both stem and progenitor cells could differentiate into hepatocytes in host livers. Repopulation efficiency and the survival period of Thy1^+, CD44^+ cells in the long term was very low. The short life of the cells may be due to their cellular senescence.