低危骨髓增生异常综合征患者间充质干细胞的生物学特性的实验研究(英文)  

In Vitro Study of Biological Characteristics of Mesenchymal Stem Cells in Patients with Low-risk Myelodysplastic Syndrome

作　　者：张翼鷟 赵丹丹[1] 韩晓蘋[1] 靳海杰[1] 达万明[1] 于力[1] 

机构地区：[1]中国人民解放军总医院血液科,北京100853

出　　处：《中国实验血液学杂志》2008年第4期813-818,共6页Journal of Experimental Hematology

基　　金：the National Natural Science Foundation,No.30672208~~

摘　　要：骨髓增生异常综合征的发病机制至今尚未明确,有研究表明MDS患者骨髓基质微环境功能的异常与其发病有关。间充质干细胞是造血微环境的重要成分,本研究拟探讨低危MDS患者间充质干细胞(MSC)的生物学特性及功能。采集低危MDS患者的骨髓标本,分离、培养和扩增MSC,观察细胞形态,进行免疫表型、成骨分化能力鉴定,检测其增殖能力及对体外造血的支持功能;用实时定量RT-PCR法测定MSC中相关细胞因子及化学趋化因子的表达,并与健康供者的MSC进行比较。结果表明:培养低危MDS患者的MSC呈典型的成纤维细胞样,细胞表达SH2(CD105),SH3(CD73),Thy-1(CD90),CD34及CD45均为阴性,诱导后可向成骨细胞分化。其体外扩增能力与与健康供者相比无显著差异(p>0.05),但体外支持造血功能较后者显著减低(p<0.05)。实时定量PT-PCR显示SDF-1基因在低危MDS患者MSC中显著高表达(p<0.01)。结论:间充质干细胞的功能异常与低危MDS患者骨髓微环境的造血调控失常相关,这为MDS发病机制的认识及治疗提供了新的思路,值得进一步探讨。The myelodysplastic syndromes （ MDS ） include a diverse groups of clonal and potentially malignant bone marrow disorders. Evidences exist that microenvironment cells from MDS marrow show functional abnormalities, which may be relevant to the incidence of such a disease. Mesenchymal stem cells （MSCs） are a very important component of hematopoietic microenvironment, This study was purposed to investigate the biological characteristics and functions of MSC derived from patients with MDS in low-risk. MSCs from bone marrow samples of 11 low-risk MDS patients were isolated, cultured and expanded. Morphology, immunophenotype and osteoblasts differentiation were analyzed, Their capacity of proliferation and hematopoietic supporting in vitro were measured. A real-time quantitative reverse transcriptase polymerase chain reaction method （RQ RT-PCR） was used for detecting the expression levels of relative cytokines and chemokines in MSC. MSCs from healthy donors were used as controls. The results showed that the culture-expanded cells from MDS patients displayed a typical fibroblast-like morphology. Cells were positive for SH2 （CD105）, SH3 （CD73）, Thy-1 （CD90）, while negative for CD34 and CD45. After induction, these cells could differentiate into osteoblasts, The proliferative ability of MSCs in MDS patients were not different from those of MSC isolated from normal bone marrow （p 〉 0.05 ）, however, their capacity of hematopoietic supporting in vitro were significantly weaker （ p 〈0.05 ）. RQ RT-PCR detection indicated that the SDF-1 gene expression level in MSCs of low-risk MDS patients was significantly higher than that in MSC derived from healthy donors （p 〈0.01 ）, It is concluded that the abnormal function of MSC influences the regulation of hemotopoiesis in the bone marrow microenvironment of MDS patients. It is worthy to further investigate the new clue in etiological mechanism and therapeutic strategies for MDS.

关 键 词：骨髓增生异常综合征 低危骨髓增生异常综合征 间充质干细胞 造血微环境 SDF-1 生物学特性 

分 类 号：R733.7[医药卫生—肿瘤]