Serum from radiofrequency-injured livers induces differentiation of bone marrow stem cells into hepatocyte-like cells.

BACKGROUND: Roles that bone marrow stem cells (BMSCs) play in liver repair after liver injury and the cell therapy for liver diseases are widely accepted. However, the availability of hepatocyte-like cells from BMSCs and possible animal diseases association with culturing in fetal calf serum (FCS) are the major limitations of clinical therapy. Therefore, this study was designed to search for a new cell source for the treatment of liver injuries through investigating whether serum from radiofrequency ablation-injured rabbit livers can induce the differentiation of BMSCs into hepatocyte-like cells.

METHODS: Serum was collected from rabbits 36 h after radiofrequency ablation (RFA) treatment of the liver. BMSCs were isolated from rabbit bone marrow and were cultured in the collected serum. Cellular morphology and cell cycle were observed. Hepatocyte markers of the differentiated cells were detected by immunohistochemistry.

RESULTS: After induction for 7 d, spindle-shaped BMSCs turned into round cells that resembled the morphology of hepatocyte-like cells. Flow cytometry showed that the percentage of cells in the S/G2/M phase was higher in the RFA group than that in the FCS group and HGF groups. This result suggests that BMSC can transform into mature cells from stem cell phase. Albumin and CK18 were considered as typical marker of hepatocytes. Following induction for 14 d, the differentiated cells expressed immunofluorescence of FITC-labeled albumin and TRITC-labeled CK18.

CONCLUSION: BMSCs treated with serum collected from radiofrequency ablation-injured livers can differentiate into hepatocyte-like cells providing a cell source to cell therapy.