Human CD34(+ )cells mobilized by granulocyte colony-stimulating factor ameliorate radiation-induced liver damage in mice

INTRODUCTION: On the basis of the recently recognized potential of hematopoietic stem cells (HSCs) to give rise to hepatocytes, we have assessed the potential of granulocyte colony-stimulating factor (G-CSF)-mobilized bone marrow-derived CD34(+ )HSCs to contribute to faster recovery and promote regeneration process after acute liver injury by radiation. METHODS: G-CSF-mobilized CD34(+ )HSCs (1 × 10(5 )cells per mouse) were injected via tail vein in the irradiated femal nonobese diabetic/severe combined immunodeficient mice. Irradiated control animals received only saline infusion. RESULTS: The mobilized CD34(+ )HSCs significantly ameliorated radiation-induced liver damage. In the liver of recipient mice killed 21 days after irradiation, human albumin(+ )Y-chromosome(+ )hepatocyte-like cells, or human cytokeratin(+ )Y-chromosome(+ )hepatocyte-like cells formed cords of hepatocytes, occupied ~30% of the 4-μm section surrounding portal tracts. Furthermore, human-specific albumin mRNA expressed in the liver and human albumin was detected in the serum only in the CD34(+ )HSC-treated mice. CONCLUSIONS: Treatment with G-CSF-mobilized CD34(+ )HSCs from bone marrow into peripheral blood could significantly promote tissue reparation after acute liver injury by radiation in mice, possibly by the ability of CD34(+ )HSCs to generate hepatocytes. So mobilization of CD34(+ )HSCs might offer a novel therapeutic approach for the treatment of radiation-induced complications after radiotherapy or other acute liver diseases in humans.