The therapeutic potential of bone marrow-derived human mesenchymal stem cells (hMSC) has recently been brought into the spotlights of many fields of research. One possible application of the approach is the repair of tissue injuries related to side effects of radiotherapy. The first challenge in cell therapy is to assess the quality of the cell and the ability to retain their differentiation potential during the expansion process. Efficient delivery to the sites of intended action is also necessary. We addressed both challenges using hMSC cultured and then infused to non-obese diabetes/severe combined immunodeficiency (NOD/SCID) mice submitted to total body irradiation. Furthermore, we tested the impact of additional abdominal irradiation superimposed to total body irradiation (TBI), as a model of local therapeutic irradiation. Our results showed that the hMSC used for transplant have been expanded without significant loss in their differentiation capacities. After transplantation into adult unconditioned mice, hMSC not only migrate in bone marrow but also into other tissues. Total body irradiation increased hMSC implantation in bone marrow and muscle and further led to engraftment in brain, heart and liver. Local irradiation in addition to TBI, increased homing of injected cells to the injured tissues and to other tissues outside the local irradiation field. Morphological recovery of irradiated tissues after MSC transplantation and/or differentiation of MSC into specific organ cell types needs to be investigated. This study suggests that using the potential of hMSC to home to various organs in response to tissue injuries might be a strategy to repair the radiation-induced damages.