Transplanted bone marrow stromal cells are not cellular origin of hepatocellular carcinomas in a mouse model of carcinogenesis

AIM: To investigate the malignant potential of hepatic stem cells derived from the bone marrow stromal cells (BMSCs) in a mouse model of chemical hepatocarcino-genesis. METHODS: BMSCs from male BALB/c mice were harvested and cultured, then transplanted into female syngenic BALB/c mice via portal vein. Hepato-carcinogenesis was induced by 6 mo of treatment with diethylnitrosamine (DEN). Six months later, the liver was removed from each treated mouse and evaluated by immunohistochemistry and fluorescence in situ hybridization (FISH). RESULTS: Twenty-six percent of recipient mice survived and developed multiple hepatocellular carcinomas (HCCs). Immunohistochemically, HCC expressed placental form of glutathione-S-transferase (GST-P) and α-fetoprotein, but did not express cytokeratin 19. Y chromosome positive hepatocytes were detected by fluorescent in situ hybridization (FISH) in the liver of mice treated with DEN after BMSCs transplantation while no such hepatocytes were identified in the liver of mice not treated with DEN. No HCC was positive for the Y chromosome by FISH. CONCLUSION: Hepatic stem cells derived from the bone marrow stromal cells have a low malignant potential in our mouse model of chemical hepatocarcinogenesis.