间充质干细胞可能通过调控免疫细胞促进再生障碍性贫血小鼠骨髓的造血功能

Transfusion of mesenchymal stem cells improve the hematopoiesis in mice with aplastic anemia by regulating immune cells

目的:探讨间充质干细胞(MSCs)影响再生障碍性贫血小鼠造血功能的可能免疫机制。方法:30只小鼠分3组,分别为单纯照射组、再障模型组、MSCs治疗组,建立再生障碍性贫血小鼠模型。单纯照射组仅经5Gy[60Co]γ射线照射,再障模型组经5Gy[60Co]γ射线照射后输注DBA/2小鼠胸腺淋巴结细胞1×106cell/只,MSCs治疗组经5Gy[60Co]γ射线照射后输注DBA/2小鼠胸腺淋巴结细胞1×106cell/只,3d后输注人骨髓MSCs1×106cell/只。观察各组小鼠外周血象、骨髓及外周血CD4+细胞、CD8+细胞、CD4+/CD8+、NK细胞变化及与造血的关系。结果:经5Gy[60Co]γ射线照射后,单纯照射组、MSCs治疗组外周血象第7d开始下降,21d血象恢复正常。再障模型组外周血象第7d开始持续性下降,至21d血象仍未恢复。照射后7d,各组小鼠间外周血CD4+细胞、CD8+细胞、CD4+/CD8+无明显差异,但MSCs治疗组NK细胞低于单纯照射组和再障模型组(P<0.05)。照射后14d3组CD4+细胞比例均明显下降,CD8+细胞则表现不同,再障模型组与MSCs治疗组CD8+细胞比例明显高于单纯照射组,至照射后21d,MSCs治疗组CD8+、NK细胞与单纯照射组相近、而模型组则明显高于单纯照射组和MSCs治疗组;MSCs治疗组小鼠股骨病理切片中脂肪细胞比例明显低于再障模型组,与单纯照射组结果一致。结论:MSCs输注可能通过调控免疫细胞影响再生障碍性贫血小鼠骨髓造血功能。

AIM：To study the possible immunologic mechanism of mesenchymal stem cells （MSCs） by which the hematopoiesis of mice with aplastic anemia （AA） is improved. METHODS：The mice model of immunomediated aplastic anemia was established. Thirty BALB/c mice were divided into 3 groups：radiation group,AA model group and MSCs group. The mice in radiation group only had processing of 5 Gy [60 Co]γ radiation. The mice in AA model group were intravenously injected with the cell suspension of thymocyte and lymphnode cell mixture （prepared from DBA/2 mice,1 × 106 cells） after 5 Gy [60Co]γ radiation. The animals in MSCs group received the same treatment as the mice in AA model group did,and afterwards was injected with 1 × 106 MSCs intravenously at 3 days. All the mice in the 3 groups were observed and analyzed the following parameters：peripheral blood cells,pathological features of bone marrow,the relation between the changes of peripheral CD4 ＋ ,CD8 ＋ ,CD4 ＋ /CD8 ＋ ,NK cells and the hematopoiesis. RESULTS：After 5 Gy [60Co]γ radiation,the peripheral blood cells in all groups decreased at 7 days,while at 21 days those in MSCs group and radiation group restored to normal but those in AA model group was still at lower level. At 7 days,the cells of CD4 ＋ ,CD8 ＋ and CD4 ＋ /CD8 ＋ in each group were similar without statistical difference,but the number of NK cells in MSCs group was quite lower than that in the other 2 groups （P 0. 05）. At 14 days,the CD4 ＋ cells in all groups were obviously decreased,while the CD8 ＋ cells in MSCs group and AA model group were significantly higher than those in radiation group. At 21 days,the CD8 ＋ and NK cells in MSCs group were quite the same as those in radiation group while those in AA model group were obviously higher compared to the other 2 groups. The number of adipose cells observed in the patho-logical slice of femoral bone in MSCs group and radiation group was no difference while that in AA model group was much higher. CONCLUSION：MSCs transfusion improves the hematopoiesis in mice with aplastic anemia by regulating the functions of immune cells.