Local irradiation enhances congenic donor pluripotent hematopoietic stem cell engraftment similarly in irradiated and nonirradiated sites

Long-term multilineage chimerism is achieved in CD45 congenic mice receiving high bone marrow doses with or without mediastinal irradiation (MI). Increased donor chimerism results in MI-treated compared with nonirradiated animals, suggesting that MI makes “space” for engraftment of donor pluripotent hematopoietic stem cells (PHSCs). We have now examined whether space is systemic or whether increased engraftment of donor marrow in locally irradiated mice is confined to the irradiated bones. While increased donor chimerism was observed in irradiated bones compared with nonirradiated bones of MI-treated animals 4 weeks following bone marrow transplantation (BMT), these differences were minimal by 40 weeks. MI-treated chimeras contained more adoptively transferable donor PHSCs in the marrow of both irradiated and distant bones compared with non-MI–treated chimeras. Similar proportions of donor PHSCs were present in irradiated and nonirradiated bones of locally irradiated mice at both 4 and 40 weeks. Irradiated bones contained more donor short-term repopulating cells than distant bones at 4 weeks, but not 40 weeks, after BMT. Our study suggests that local proliferation of donor PHSCs in mice receiving local irradiation rapidly leads to a systemic increase in donor PHSC engraftment.

Erythrocyte Fe59 Uptake as a Function of Bone Marrow Dose Injected in Lethally Irradiated Mice

The relation between bone marrow cell dose and 24-hour erythrocyte Fe59 uptake has been established in lethally irradiated mice. Erythrocyte Fe59 uptake is a function of the dose of bone marrow cells and of the time after irradiation at which Fe59 is injected. By choosing appropriate bone marrow doses and times of Fe59 injection, the range of cell doses between 5 x 105 and 2 x 107 has been explored. The relation between cell dose and Fe59 uptake is linear for Fe59 uptakes between 0 to 30 per cent. The steepest line relating Fe59 uptake to cell dose is that obtained when Fe59 was injected at day 9 and covers the range of 5 X 104 to 5 X 105 cells. The curve obtained when iron is injected on day 5 is much flatter and covers the range of 1 x 106 to 2 x 107 cells. Erythropoiesis stimulating factor (ESF) in doses that stimulate erythrocyte Fe59 uptake in normal mice has no effect in irradiated, bone marrow-treated mice. Homologous marrow is slightly less effective, and rat bone marrow markedly (∼ 100 times) less effective in promoting recovery of erythropoieis. The erythrocyte Fe59 uptake of mice preimmunized with homologous or rat marrow before irradiation is much lower than that of nonpreimmunized animals.