Abstract
To clarify the mechanisms of graft failure after umbilical cord blood transplantation, we examined the effects of myeloablative conditioning equivalent irradiation on bone marrow stromal cells. When murine bone marrow stromal HESS-5 cells were irradiated with over 10 Gy, expression of stromal cell-derived factor-1 (SDF-1) and Jagged-1 mRNA was decreased significantly compared with non-irradiated cells. SDF-1 protein was also decreased in culture media supernatant from irradiated HESS-5 cells. Co-culture experiments of irradiated HESS-5 cells with human cord blood CD34+ cells revealed that irradiation up to 20 Gy did not affect the proliferative ability and supporting ability for cord blood CD34+ cells. When HESS-5 cells were irradiated with over 10 Gy, the culture media supernatant obtained from the irradiated cells exhibited diminished chemotactic activity towards umbilical cord mononuclear cells compared with that from non-irradiated cells. In addition, whole-body irradiation with over 10 Gy in mice resulted in an approximate 10% reduction in the number of bone marrow stromal cells. Whole-body irradiation with over 10 Gy also decreased the expression of SDF-1 in bone marrow stroma. Taken together, we demonstrated that myeloablative conditioning equivalent irradiation leads to a decrease in the number of bone marrow stromal cells and the expression of SDF-1. These data suggest that whole-body irradiation for myeloablative conditioning may contribute to graft failure after umbilical cord blood transplantation.
