Department of Haematology and Transplantation, Affiliated Hospital of Academy of Military Medical Sciences, Beijing, China.
Br J Radiol. 2010 Jan;83(985):52-8. doi: 10.1259/bjr/61042310.
The aim of this study was to investigate the effects and mechanisms of mesenchymal stem cells (MSCs) on haematopoietic reconstitution in reducing bone marrow cell apoptosis effects in irradiated mice, and to research the safe and effective dosage of MSCs in mice with total body irradiation (TBI). After BALB/c mice were irradiated with 5.5 Gy cobalt-60 gamma-rays, the following were observed: peripheral blood cell count, apoptosis rate, cell cycle, colony-forming unit-granulocyte macrophage (CFU-GM) and colony-forming unit-fibroblast (CFU-F) counts of bone marrow cells and pathological changes in the medulla. The survival of mice infused with three doses of MSCs after 8.0 Gy or 10 Gy TBI was examined. The blood cells recovered rapidly in the MSC groups. The apoptotic ratio of bone marrow cells in the control group was higher at 24 h after radiation. A lower ratio of G0/G1 cell cycle phases and a higher ratio of G2/M and S phases, as well as a greater number of haematopoietic islands and megalokaryocytes in the bone marrow, were observed in the MSC-treated groups. MSCs induced recovery of CFU-GM and CFU-GM and improved the survival of mice after 8 Gy TBI, but 1.5 x 10(8) kg(-1) of MSCs increased mortality. These results indicate that MSCs protected and treated irradiated mice by inducing haematopoiesis and reducing apoptosis. MSCs may be a succedaneous or intensive method of haematopoietic stem cell transplantation under certain radiation dosages, and could provide a valuable strategy for acute radiation syndrome.
本研究旨在探讨间充质干细胞(MSCs)对造血重建的影响及其机制,以减轻照射小鼠骨髓细胞凋亡的作用,并研究全身照射(TBI)小鼠中 MSCs 的安全有效剂量。在 BALB/c 小鼠接受 5.5 Gy 钴-60 γ射线照射后,观察外周血细胞计数、骨髓细胞凋亡率、细胞周期、集落形成单位-粒细胞巨噬细胞(CFU-GM)和集落形成单位-成纤维细胞(CFU-F)计数以及骨髓的病理变化。检查输注三种剂量 MSCs 后 8.0 Gy 或 10 Gy TBI 小鼠的存活情况。MSC 组的血细胞迅速恢复。照射后 24 小时,对照组骨髓细胞的凋亡比例较高。MSCs 处理组的 G0/G1 细胞周期比例较低,G2/M 和 S 期比例较高,骨髓中的造血岛和巨核细胞较多。MSCs 诱导 CFU-GM 和 CFU-GM 的恢复,并提高 8 Gy TBI 后小鼠的存活率,但 1.5 x 10(8) kg(-1) 的 MSCs 增加了死亡率。这些结果表明,MSCs 通过诱导造血和减少凋亡来保护和治疗照射小鼠。MSCs 可能是在一定辐射剂量下替代或强化造血干细胞移植的方法,并为急性辐射综合征提供有价值的策略。