Microvesicles as Potential Biomarkers for the Identification of Senescence in Human Mesenchymal Stem Cells.
Microvesicles as Potential Biomarkers for the Identification of Senescence in Human Mesenchymal Stem Cells.
复制标题
微泡作为鉴定人间充质干细胞衰老的潜在生物标志物
作者：
Lei Q;Liu T;Gao F;Xie H;Sun L;Zhao A;Ren W;Guo H;Zhang L;Wang H;Chen Z;Guo AY;Li Q
人骨髓间充质干细胞（mesenchymal stem cells，MSCs）的衰老不仅导致机体衰老和多种疾病的发生，而且严重影响其作为一种有前途的细胞治疗方法的治疗性能。寻找代表细胞衰老的有效生物标志物的研究引起了人们的广泛关注;然而，目前没有单一的标志物提供细胞衰老的准确的无细胞表示。在这里，我们研究了MSC衍生的微泡（MSC-MV）的特征，这些特征可能反映了其亲本MSC的衰老。我们发现，衰老的晚代（LP）MSC分泌更高水平的MSC-MVs，尺寸比早代（EP）MSC小，并且亲本MSC中CD 105 + MSC-MVs的水平随着衰老而下降。此外，在LP中观察到的促进MSC成骨的能力明显弱于EP MSC-MV。RNA测序的比较分析显示，在MSC和MSC-MV中，随着传代次数的增加，高表达的miRNA数量减少的趋势相同。LP MSCs和相应的MSC-MV中的大多数高表达基因参与了衰老相关疾病的调控，如阿尔茨海默病。此外，基于MSC衰老过程中的miRNA谱、转录因子（TF）和基因调控网络，以及GEO数据库中的数据，我们证实MSC-MV中miR-146 a-5 p的表达与其亲本MSC的衰老状态相似。我们的研究结果提供的证据表明，MSC-MV是一个关键因素，在衰老相关的分泌表型的MSC，并证明其综合特征可以动态地反映代表一个潜在的生物标志物监测MSC衰老的MSC的衰老状态。
Senescence in human mesenchymal stem cells (MSCs) not only contributes to organism aging and the development of a variety of diseases but also severely impairs their therapeutic properties as a promising cell therapy. Studies searching for efficient biomarkers that represent cellular senescence have attracted much attention; however, no single marker currently provides an accurate cell-free representation of cellular senescence. Here, we studied characteristics of MSC-derived microvesicles (MSC-MVs) that may reflect the senescence in their parental MSCs. We found that senescent late passage (LP) MSCs secreted higher levels of MSC-MVs with smaller size than did early passage (EP) MSCs, and the level of CD105+ MSC-MVs decreased with senescence in the parental MSCs. Also, a substantially weaker ability to promote osteogenesis in MSCs was observed in LP than EP MSC-MVs. Comparative analysis of RNA sequencing showed the same trend of decreasing number of highly-expressed miRNAs with increasing number of passages in both MSCs and MSC-MVs. Most of the highly-expressed genes in LP MSCs and the corresponding MSC-MVs were involved in the regulation of senescence-related diseases, such as Alzheimer's disease. Furthermore, based on the miRNA profiling, transcription factors (TF) and genes regulatory networks of MSC senescence, and the datasets from GEO database, we confirmed that expression of miR-146a-5p in MSC-MVs resembled the senescent state of their parental MSCs. Our findings provide evidence that MSC-MVs are a key factor in the senescence-associated secretory phenotype of MSCs and demonstrate that their integrated characteristics can dynamically reflect the senescence state of MSCs representing a potential biomarker for monitoring MSC senescence.
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影响因子：
4.8
作者：
Akyurekli, Celine;Le, Yevgeniya;Allan, David S.
通讯作者：
Allan, David S.
DOI：
10.1097/qai.0000000000000756
发表时间：
2015-11-01
期刊：
Journal of acquired immune deficiency syndromes (1999)
影响因子：
--
作者：
Hubert A;Subra C;Jenabian MA;Tremblay Labrecque PF;Tremblay C;Laffont B;Provost P;Routy JP;Gilbert C
通讯作者：
Gilbert C
影响因子：
64.8
作者：
Baker DJ;Childs BG;Durik M;Wijers ME;Sieben CJ;Zhong J;Saltness RA;Jeganathan KB;Verzosa GC;Pezeshki A;Khazaie K;Miller JD;van Deursen JM
通讯作者：
van Deursen JM
影响因子：
64.5
作者：
de Cabo R;Carmona-Gutierrez D;Bernier M;Hall MN;Madeo F
通讯作者：
Madeo F
雷帕霉素通过抑制 mTOR 信号通路来逆转衰老表型并改善 MRL/lpr 小鼠和系统性红斑狼疮患者间充质干细胞的免疫调节。
DOI：
10.18632/aging.100925
发表时间：
2016-05
期刊：
Aging
影响因子：
--
作者：
Gu Z;Tan W;Ji J;Feng G;Meng Y;Da Z;Guo G;Xia Y;Zhu X;Shi G;Cheng C
通讯作者：
Cheng C