成人骨髓源性神经干细胞高迁移能力的基因分析

Genetic analysis of adult human bone marrow-derived neural stem cells with strong migration potential

目的检测成人骨髓源性神经干细胞（Md—NSCs）中与细胞侵袭转移相关基因的表达情况．研究Md-NSCs在中枢神经系统中具有高迁移能力的基因基础。方法自正常成人志愿者获取成人骨髓基质细胞（BMSCs），于体外诱导培养获得Md-NSCs，应用寡核苷酸基因芯片检测Md—NSCs中与细胞侵袭转移相关基因的表达情况；应用实时定量PCR（RT—PCR）检测验证基因芯片的结果。结果基因芯片检测结果显示，与新鲜正常成人骨髓细胞去红细胞相比较，Md—NSCs中与细胞侵袭转移相关基因（MMP1、MMP2、MMP17、ITGA3、RhoB、RhoC及RhoD）均呈高度表达；RT-PCR检测结果显示．MMP2、ITGA3、RhoC在Md-NSCs中高度表达，分别为新鲜正常成人骨髓细胞去红细胞含量的2．84×10^0倍、2．22×10^2倍及4．92×10^0倍。结论Md—NSCs在中枢神经系统中具有高迁移能力可能与该细胞中促进细胞侵袭转移相关基因的高度表达相关。另外，这些高度表达的基因属于重要的癌基因，因此对Md—NSCs致瘤性问题的深入研究值得重视。

Objective To analyze the gene expression profiles in relation to the migration ability of adult human bone marrow-derived neural stem cells （Md-NSCs）, and identify the genetic basis of the high migration potential of Md-NSCs in the central nervous system （CNS）. Methods Adult human bone marrow stromal cells（BMSCs） obtained from adult healthy volunteers were induced to differentiate into Md-NSCs in vitro, and the expressions of the genes related to cell invasiveness and metastasis were investigated by microarray analysis. Quantitative real-time PCR （RT-PCR） was used to verify the mieroarray results. Results The results of microarray analysis revealed significant overexpressions of the genes MMP1, MMP2, MMP17, ITGA3, RhoB, RhoC and RhoD in the Md-NSCs as compared with the expressions in fresh normal human adult bone marrow cells depleted of red blood cells. Quantitative RT- PCR verified the overexpression ofMMP2 gene by 2.84×10^0 folds, 1TGA3 gene by 2.22×10^2folds, and RhoC gene by 4.92×10^0folds. Conclusion The high migration potential of the Md-NSCs in the CNS is probably associated with the overexpression of the genes that promote cell invasiveness and metastasis. These overexpressed genes are also important oncogenes, and therefore the tumorigenicity of the Md-NSCs warrants further investigation.