Experimental study of low dose irradiation for treatment of immuno-mediated aplastic anemia in mice / 中国实验血液学杂志

ABSTRACT

As the lymphocytes of immuno-mediated aplastic anemia (IMAA) are in active state, and the hematopoietic stem cells are in silence, this study was aimed to design a new strategy to treat IMAA. To utilize the difference of radiosensitivity between active lymphocytes and silent hematopoietic stem cells, the animals suffered from IMAA were treated with a single low dose of irradiation, killing the active lymphocytes to release its suppression to hematopoietic stem cells without injuring the hematopoietic stem cells. Therefore, the hematopoiesis can be restored. Experiments were completed in IMAA mouse model. At day 4 after making IMAA, the model mice were giren total body irradiation of 150 cGy, the non-treated model mice and normal mice irradiated with 150 cGy were used as control. The survive time and survive rate of mice, blood picture, the account of nucleated cell of bone marrow, and pathological changes of bone marrow and lymphoid tissues of each group mice were observed. The results were as follows (1) Survive rate of IMAA mice in non-treated group was 12.5%, the average survive time was 27.4 +/- 13.4 days. 100% of IMAA mice in irradiation-treated group survived over 60 days. The mice of irradiation control group all survived. (2) The account of WBC of IMAA mice in non-treated group dramatically decreased until to die, and in the irradiation-treated group it was gradually increased since the 10th day after treatment and close to normal level at the 28th day. (3) The RBC hematocrit of IMAA mice in non-treated group progressively decreased at day 14, and IMAA mice of irradiation-treated group gradually recovered closely to normal level after slightly fall at day 14, similar to the mice of irradiation control group. (4) The account of nucleated cells of bone marrow in non-treated IMAA mice dramatically decreased, and in the IMAA mice of the irradiation-treated group it was rapidly increased following transient fall, and restored to normal. (5) Pathological observations showed that the bone marrow and spleen of non-treated IMAA mice demonstrated typical aplastic anemia pattern, including bone marrow failure, marked splenatrophy, but the bone marrow and lymphoid tissues in the IMAA mice of irradiation-treated group were recovered to normal at day 28 after treatment. It is concluded that the low dose of irradiation displayed a significant therapeutic effect to IMAA mice, their hematopoisis could be completely restored to normal. The mechanism of therapeutic effect may contribute to low dose of irradiation killing the immunocompetent lymphocytes, therefore, suppressing hematopoiesis. The experiment results not only set up a new strategy for IMAA treatment, but also provided a clue to study the mechanism of IMAA.