摘要
骨髓乏氧环境对完整保持骨髓造血干/祖细胞(bone marrow hematopoietic stem cells,BMHSC)是适宜的。外周血干细胞移植(peripheral blood stem cell transplantation,PBSCT)中,外周HSC常氧下体外扩增及移植前后,HSC暴露于浓度差别显著的氧环境下,HSC的生物学功能是否受到影响值得研究。本研究模仿人外周血造血干细胞移植(peripheral blood hematopoietic stem cell transplantation,PBHSCT)中BMHSC所经历的氧环境,通过体外扩增及凋亡实验、细胞周期分析及定向分化实验、细胞迁徙实验等来研究氧浓度变化对人BMHSC生物功能的影响。结果表明:浓度低于常氧,特别是乏氧的氧环境能使BMHSC扩增更多的较原始的AC133+CD34+HSC和有活性的CD34+HSC,维持较多的干细胞处于G0/G1期,促进各系集落(BFU-E、CFU-GM、CFU-GEMM)的生长,更好地维持HSC的迁徙能力。而暴露于常氧、不恒定且氧浓度变化剧烈的氧环境中的BMHSC,上述功能指标都较低。结论:PBSCT中BMHSC的生物功能与细胞周围氧环境中氧浓度高低及稳定性密切相关,在浓度较低的氧环境下培养BMHSC可能对PBSCT更有益。
Hypoxia in bone marrow is suitable for the perfect preservation of biological functions of bone marrow hematopoietic stem cells （BM HSC）. It is deserved to study whether the biological functions of BM HSC are influenced when being exposed to environment of oxygen at various concentration during amplification of BM HSCs in normal oxygen condition in vitro and process of peripheral blood hematopoietic stem cell transplantation（PBSCT）. This study was purposed to investigate the effects of various oxygen concentrations on biological functions of human BM HSCs. The BM HSCs were amplified in vitro, the amplification level of CD34^＋ HSCs and CD34^＋ AC133^＋ HSCs were detected by flow cytometry, the apoptosis and cell cycle distribution of CD34^＋ HSCs amplified in various oxygen concentrations were assayed by flow cytometry with Annexin V/PI double staining as well as PI and Ki-67 antibody, respectively, the differentiation of amplified CD34^＋ HSCs in vitro was determined by direction differentiation assay, the migration ability of amplified CD34^＋ AC133^ ＋ HSCs was measured by migration test. The results indicated that the oxygen environment below normal oxygen, especially hypoxia, could amplify more primitive CD34^＋ AC133^＋ HSCs and CD34^＋ HSCs with activity, arrest more HSCs in G0/G1 phase, promote the generation of BFU-E, CFU-GM, CFU-GEMM, and better preserve the migration ability of HSCs. While the above functional indicators of BM HSCs were poor when HSCs exposed to normoxia, oxygen-unstable and oxygen-severe changeable environments. It is concluded that the biological functions of BM HSCs in PBSCT are related with oxygen concentration and its stability, the culture of BM HSCs in lower oxygen environment may be more beneficial for PBSCT.
出处
《中国实验血液学杂志》
CAS
CSCD
2010年第4期997-1001,共5页
Journal of Experimental Hematology
基金
辽宁省教育厅科研项目
编号2009A714
关键词
氧浓度
骨髓
造血干细胞
生物功能
oxygen concentration
bone marrow
hematopoietic stem cell
biological function
