氧浓度、活性氧和鼠骨髓造血干细胞生物特性三者之间关系的研究

发布时间：2019-05-08 21:25

【摘要】：目的:模似人外周血干细胞移植(peripheral blood stem cell transplantation,PBSCT)中PBHSC所经历的氧环境,探讨氧浓度和活性氧对骨髓HSC生物特性的影响。方法:采用活性氧(reactive oxygen species,ROS)测定、体外扩增实验、定向分化实验、细胞迁徙实验、亚致死量射线辐照NOD/SCID小鼠CFU-S和归巢黏附分子表达测定以研究氧浓度及活性氧对小鼠骨髓造血干细胞生物学特性的影响及三者之间的关系。结果:氧浓度低于常氧,特别是乏氧的氧环境能降低ROS的产生扩增更多Lin~-c-kit~+Sca-1~+BM HSC,更有利于各系集落(BFU-E、CFUGM、CFU-Mix)的生长,更多地表达归巢黏附分子(CXCR4、CD44、VLA4、VLA5、P-selectin),因而更好地维持了HSC的迁徙能力,并明显促进亚致死量射线辐照NOD/SCID小鼠移植后的脾集落(CFU-S)生长;而暴露于常氧、不恒定且氧浓度变化剧烈的氧环境中的BM HSC能产生较高水平的活性氧,上述特征和功能指标都较低。结论:PBSCT中BM HSC的ROS水平与周围氧环境中氧浓度高低及稳定性密切相关,高浓度氧产生高水平的ROS高水平的ROS不利于BM HSC生物学特性的保持。在PBHSCT移植前后和体外扩中有目的地应用抗氧化剂和在恒定的浓度较低的氧环境下培养可能对BM HSC移植更有益。
[Abstract]:Aim: to investigate the effects of oxygen concentration and reactive oxygen species (Ros) on the biological characteristics of human peripheral blood stem cell transplantation (peripheral blood stem cell transplantation,PBSCT) by simulating the oxygen environment experienced by PBHSC in human peripheral blood stem cell transplantation (PBSC). Methods: reactive oxygen species (Ros) (reactive oxygen species,ROS), in vitro amplification test, directional differentiation test and cell migration test were used. The effects of oxygen concentration and reactive oxygen species (Ros) on the biological characteristics of bone marrow hematopoietic stem cells (BMSCs) in NOD/SCID mice irradiated by sublethal dose radiation were studied by measuring the expression of CFU-S and NCAM in order to study the relationship among them. Results: oxygen concentration was lower than normal oxygen, especially hypoxia oxygen environment could reduce the production of ROS and expand more Lin~-c-kit~ Sca-1~ BM HSC, which was more beneficial to the growth of BFU-E,CFUGM,CFU-Mix. More homing adhesion molecules (CXCR4,CD44,VLA4,VLA5,P-selectin) were expressed, so the migration ability of HSC was better maintained, and the growth of spleen colony (CFU-S) after sublethal radiation irradiation in NOD/SCID mice was significantly promoted. However, BM HSC exposed to normoxic, unstable and highly varying oxygen concentration could produce a higher level of reactive oxygen species (Ros), and the above characteristics and functional indexes were lower. Conclusion: the ROS level of BM HSC in PBSCT is closely related to the concentration and stability of oxygen in the surrounding oxygen environment. High concentration of oxygen produces high level of ROS and high level of ROS is not conducive to the maintenance of biological characteristics of BM HSC. Targeted application of antioxidants before and after PBHSCT transplantation and in vitro expansion and culture in a constant concentration of oxygen may be more beneficial to BM HSC transplantation.
【作者单位】：中国医科大学附属第一医院输血科;
【基金】：沈阳市科学技术项目(F11-264-1-12)
【分类号】：R457.7

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