Involvement of the bone marrow stroma in the residual hematopoietic damage induced by irradiation of adult and young mice.

The analysis of femoral hematopoiesis of mice irradiated with 7 Gy x-rays at the age of 1 and 12 weeks evidenced a differential hematopoietic dysfunction in the long term. Significant hematopoietic damage was observed 1 year after irradiation of 12-week-old mice: a marked reduction in the number of hematopoietic progenitors and a severe impairment in the self-renewal capacity of the colony-forming unit-spleen (CFU-S) population. In the case of the 1-week-old irradiated mice, normal values in the femoral hematopoietic progenitors were observed, although a significant impairment in the capacity for self-renewal of the CFU-S population was apparent. The role that the stromal cells played in these hematopoietic failures was investigated by ectopic implantation of bone marrow from the irradiated animals into the renal capsule of nonirradiated mice. Bone marrow implants from both types of donor-irradiated mice developed ossicles that were incapable of sustaining normal values of host hematopoietic progenitors, thus indicating that radiation mediated long-term damage in the hematopoietic lodging capacity of the stromal cells. However, analysis of the number of CFU-S generated per ossicle-derived spleen colony revealed that the irradiation of hematopoietic stromas resulted in an improved self-renewal capacity of lodged unirradiated CFU-S precursors. Our data strongly suggest that the impairment in the long-term self-renewal capacity of the CFU-S population is not a result of the stromal damage. Rather, this stromal damage might actually generate a stimulatory response facilitating the preservation of the low numbers of primitive precursors that survived the irradiation.