Differentiation of Hematopoietic Stem Cells into Hepatocytes in Liver Fibrosis in Rats

It has been reported that hematopoietic stem cells (HSC) can differentiate into hepatocytes in the normal liver and in some pathologic environments. The aim of this study was to investigate whether HSC can differentiate into hepatocytes in cases of established liver fibrosis. Rat liver fibrosis was induced by subcutaneous injection of tetrachloride (CCl4). Thy+CD3−CD45RA− HSC in bone marrow cells, which had been enriched by fluorescence- activated cell sorting (FACS), were labeled with PKH26-GL, and autologously transplanted into CCl4-treated rats. The expressions of albumin (Alb), cytokeratin 8 (CK8), and α-smooth muscle actin (SMA) were determined by immunofluorescence methods. The PKH26-GL labeled Thy+CD3−CD45RA− HSC expressed the hepatocyte-specific markers Alb and CK8, but did not express α-SMA in liver fibrosis. Thy+CD3−CD45RA− HSC differentiated into hepatocytes, but not into hepatic stellate cells. In conclusion, autologous stem cell transplantation may be helpful to treat hepatic fibrosis.