摘要
本研究旨在探讨骨髓增生异常综合征(MDS)患者与正常对照者造血细胞(HC)及经分离所得骨髓间充质干细胞(BMMSC)的细胞遗传学特征,分析其是否同时受累并参于MDS的发病及进展。收集我院血液科收治初诊的22例MDS患者及7例体检者(正常对照)骨髓,建立贴壁培养体系,分离并体外扩增BMMSC。根据形态学特征及流式细胞仪检测的表面抗原进行鉴定,初步分析MDS患者的BMMSC的细胞特征。进一步对HC和BMMSC同时进行胰酶-Giemsa技术(GTG)显带,根据ISCN(2005)要求,进行核型分析,并比较两者间的细胞遗传学特征。结果表明,本研究组成功建立了体外培养分离扩增体系。经光学显微镜及流式细胞仪鉴定证实,MDS患者的BMMSC具有典型的细长纺锤形的形态学特征及表达CD29、CD73、CD90,不表达CD34、CD45非造血细胞的抗原特征。MDS患者BMMSC也存在细胞染色体畸变(64%),以染色体物质不平衡畸变多见,尤其是缺失较为多见(92%),其中克隆性缺失7例,占50%。研究发现有高比例的随机丢失,不排除是其遗传学不稳定性的特征。HC与BMMSC间没有出现完全一致的畸变类型,HC正常核型的MDS患者中有5例存在畸变(33%),畸变率显著低于HC异常核型患者(92%)。结论:MDS患者BMMSC存在细胞遗传学异常。染色体物质不平衡畸变可能是其遗传学不稳定的标记,非造血起源的BMMSC显示有别于HC的畸变类型,提示两者遗传易感性相似但不完全相同。研究BMMSC在MDS发病机制中的潜在作用,有助于我们进一步认识该疾病生物学特征,为MDS的诊断及治疗提供新的途径。
This study was aimed to investigate the cytogenetic characteristics of hematopoietic cells（HC） and bone marrow mesenchymal stoma cells（BMMSC） isolated from patients with myelodysplastic syndrome（MDS） and healthy individuals as normal controls,and to clarify whether HC and BMMSC are simultaneously involved and participate in pathogenesis and development of MDS.Both marrows of 22 newly diagnosd patients with MDS and 7 healthy individuals were collected;BMMSC were isolated and amplified by using established culture system,as well as were identified according to morphologic features and surface antigens detected by flow cytometry;the characteristics of BMMSC from MDS patients were analyzed;the BMMSC karyotyping analysis of MDS patients was performed by banding of HC and BMMSC with pancreatin-Giemsa technique（GTG） and in accordance with ISCN（2005） requirements;the cytogenetic charactaristics of HC and BMMSC were compared.The results showed that in vitro culture system for isolation and amplification was successfully established.The light microscopy and flow cytometry confirmed that BMMSC possessed characteristics showing long and thin splindle form and expressing CD29,CD73,CD90 antigens,and unexpressing CD34,CD45 antigens.In BMMSC of 14 MDS patients（64%）,the cytogenetic abnormalities were found usually involving the loss of chromosomal material（92%）,among which clonal loss was observed in 7 cases（50%）.The detection indicated a random loss of chromosomal material in significant proportion of BMMSC.A high proportion of chromosomal material random loss may be a marker of chromosomal instability in BMMSC of MDS patients,the detection also showed that completely consistent aberration types did not exist between HC and BMMSC.The aberrations wereobserved in 3 cases of MDS with normal karyotype of HC,its aberration rate（33%）was obviously lower than that inMDS patients with abrromal karyotypes（92%）.It is concluded that the cytogenetic abnormalities exist in BMMSC ofMDS patients,the unbalanced aberration of chromosomal materials may be a genetic instability marker of BMMSC.Thedifference of aberration types in BMMSC from HC sugests that genetic susceptibility of BMMSC and HC is similar,butno completely identical,which indicates the potential involvement of BMMSC in pathogenesis of MDS.Studing thispotential role of BMMSC can be helpful to further understanding of MDS biological characteristics and provide the newapproaches for diagnosis and therapy of MDS.
出处
《中国实验血液学杂志》
CAS
CSCD
2011年第2期372-378,共7页
Journal of Experimental Hematology
基金
上海交通大学附属第六人民医院院级科研基金项目,编号11004
