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。
Objective:To investigate the effects of oxygen concentration and reactive oxygen species(ROS) on the biological characteristics of hematopoietic stem cells(HSC) and to analyzed the relationship among the oxygen concentration,ROS and the biological characteristics of mouse HSC through simulation of oxygen environment experienced by PB HSC during transplantation.Methods:The detection of reactive oxygen species(ROS),in vitro amplification,directional differentiation(BFU-E,CFU-GM,CFU-Mix),homing of adhesion molecules(CXCR4,CD44,VLA4,VLA5,P-selectin),migration rate,CFU-S of NOD/SCID mice irradiated with sublethal dose were performed to study the effect of oxgen concentration and reactive oxygen species on the biological characteristics of mouse BM-HSC and the relationship among them.Results:The oxygen concentrations lower than normal oxygen concentration(especially hypoxic oxygen environment) could reduce ROS level and amplify more Lin^-c-kit^+ Sca-1^+ BM HSC,which was more helpful to the growth of various colonies(BFU-E,CFU-GM,CFU-Mix) and to maintain the migratory ability of HSC,thus promoting CFU-S growth significantly after the transplantation of HSC in NOD/SCID mice irradiated by a sublethal dose.BM HSC exposed to oxygen environments of normal,inconstant oxygen level and strenuously thanging of oxygen concentration could result in higher level of ROS,at the same time,the above-mentioned features and functional indicators were relatively lower.Conclusion:The ROS levels of BM HSC in PB HSCT are closely related to the concentrations and stability of oxygen surrounding the cells.High oxygen concentration results in an high level of ROS,which is not helpful to maintain the biological characteristics of BM HSC.Before transplantation and in vitro amplification,the application of antioxidancs and constant oxygen level environments may be beneficial for transplantation of BMMSC.
出处
《中国实验血液学杂志》
CAS
CSCD
北大核心
2016年第1期205-210,共6页
Journal of Experimental Hematology
基金
沈阳市科学技术项目(F11-264-1-12)
关键词
活性氧
氧浓度
骨髓
造血干细胞
生物特性
reactive oxygen species
oxygen concentration
bone marrow
hematopoietic stem cell
biological characteristics
