Degeneration of Stroma Reduces Retention of Homed Cells in Bone Marrow of Lethally Irradiated Mice

Abstract

Cytotoxic drugs or irradiation are generally administered before bone marrow (BM) transplantation because of the idea that host bone marrow 'niches' become available to the donor cells for engraftment. How BM stromal cells respond to the radiation, which ultimately modulates grafting of donor cells, is poorly understood. In this study, we examined homing and marrow retention of PKH26⁺ donor cells in BM of age-matched C57BL/6J mice conditioned at different doses of irradiation. When we injected donor cells into mice that received 900 cGy, the percent homing was highest (15.8 ± 1.5%) as compared to the lower doses of radiation. Despite the highest levels of homing of donor cells in these mice, about 70% (p < 0.005) homed cells were detached from the marrow within 72 h of transplantation. In contrast, a 2- to 2.5-fold (p < 0.03) multiplication of homed PKH-26⁺ Sca-1⁺ cells was observed in sublethally irradiated mice. While determining that CD45^- CD106⁺ cells in BM of the mice received 900 cGy, we found that more than 80% of cells were depleted. It was also revealed from this investigation that grafted cells conferred partial protection to the endogenous myeloid colony-forming cells from radiation injury. Collectively, the present study implicates radiation-induced degeneration of stroma as a cause of poor retention of donor cells in BM of lethally irradiated mice. These results may have important clinical implications in designing conditioning regimens for BM transplantation.