人骨髓间充质干细胞对放射损伤小鼠造血恢复的影响

本研究旨在探讨人骨髓间充质干细胞(hBMMSC)对受γ射线照射小鼠造血恢复的影响。亚致死剂量(6Gy)60Co-γ射线全身照射雌性BALb/c小鼠,静脉输注不同剂量(1×105,1×106和5×106)的hBMMSC,观察注射后小鼠血常规指标、骨髓造血祖细胞集落量以及血清人TPO,SCF和G-CSF水平等动态变化。结果表明:hBMMSC输注对亚致死量照射小鼠早期死亡率无影响;与对照组比较,接受细胞治疗小鼠早期血象水平无显著增高,但在第28天外周血白细胞、红细胞、血小板计数和血红蛋白水平高于对照组,尤以大剂量组明显(P值均小于0.05);在中剂量和大剂量hBMMSC组小鼠骨髓中,单个核细胞集落形成单位总数和粒单系集落形成单位数均高于对照组(P<0.05);hBMMSC输注后第2天,ELISA法检测可在细胞治疗组小鼠血清中检测到人G-CSF和SCF,以hBMMSC高剂量组G-CSF含量为最高(P<0.01)。所有各组未检测到人TPO,治疗后第9和16天所有各组血清中均未检测到人G-CSF和SCF。结论:hBMMSC输注可加速放射损伤小鼠造血功能的恢复,其机制可能与细胞短暂分泌相关造血细胞调控因子有关。

Effect of Human Bone Marrow Mesenchymal Stem Cell Transplantation on Hematopoietic Recovery of Irradiated Mice

This study was aimed to investigate the effect of human bone marrow mesenchymal stem cells （hBMMSC） on the hematopoietic recovery of sublethally irradiated mice. Female BALb/c mice irradiated with ^60Coγ ray at a single dose of 6 Gy received graded doses of hBMMSC（1×10^5,1×10^6 and 5×10^6） by intravenous infusion. The counts of leukocytes, platelets, erythrocytes and hemoglobin level in peripheral blood, the amount of bone marrow hematopoietic progenitors, and the serum levels of human TPO, SCF and G-CSF as well were evaluated at different time points after transplantation. The results showed that hBMMSC infusion had little protective effect on the survival of irradiated mice. Compared with the control mice, the peripheral blood cell counts of hBMMSC-treated mice were not obviously elevated during 3 weeks after infusion, however, blood cell counts were significantly greater at 4 weeks after cell treatment （ P 〈 0.05 ）. The amount of colony-forming unit of mononuclear cells and granulocyte/monocytes in bone marrow of mice that received middle and high doses of hBMMSC were dramatically greater than that in control mice （ P 〈0.05 ）. Two days after hBMMSC administration, human G-CSF and SCF could be detected in the sera from hBMMSC-treated mice, and the G-CSF concentration of mice that received high-dose hBMMSC was significantly higher than that in other groups （P 〈 0.01 ）. Nevertheless, human TPO was undetectable in the sera of all mice tested and serum human G-CSF and SCF could not be detected on days 9 and 16 in all groups. It is concluded that hBMMSC maypromote the hematopoietic recovery of irradiated mice, probably by transient secretion of hematopoiesis-associated factors by the implanted ceils.