Paracrine action of mesenchymal stem cells revealed by single cell gene profiling in infarcted murine hearts.
Paracrine action of mesenchymal stem cells revealed by single cell gene profiling in infarcted murine hearts.
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DOI：
10.1371/journal.pone.0129164
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Ma C
中科院分区：
文献类型：
--
作者：
Yao Y;Huang J;Geng Y;Qian H;Wang F;Liu X;Shang M;Nie S;Liu N;Du X;Dong J;Ma C
骨髓间充质干细胞（MSCs）是近年来发现的一种有前途的干细胞类型，可以挽救急性心肌梗死后受损的心肌。其治疗作用的最重要机制之一是旁分泌因子的分泌。然而，在梗死的心脏，特别是在单细胞水平上的MSC的旁分泌因子的表达谱，是很差的定义。我们的目的是描绘的旁分泌因子在体内由骨髓间充质干细胞分泌的转录谱，特别是在正常和梗死心脏之间的比较感兴趣。分离骨髓间充质干细胞，并在梗死手术后立即注射到小鼠心脏中。生物发光成像（BLI）表明，即使在手术后10天，仍有一定比例的细胞存活。MRI和组织学显示，与PBS注射小鼠相比，MSC注射后存活细胞的心脏功能显著改善。尽管MSC注射心脏中血管数量增加，但在梗死后5天的梗死心脏中未观察到内皮细胞和心肌细胞转分化。此外，在我们的研究中，采用激光捕获显微切割（LCM），然后进行高通量真实的时间PCR，发现注射的MSC，与局部心肌细胞相比，显示分泌因子水平升高。为了进一步研究这些因子的调节，我们进行了单细胞分析，分别在梗死和正常心脏中在单细胞水平上解剖MSC的基因表达谱。与体内观察一致，在缺氧条件下培养的MSC中检测到这些因子的类似调节模式。我们的研究，首次阐明了基因表达谱，以及调节旁分泌因子，在单细胞水平的骨髓间充质干细胞在体内，表明旁分泌因子从骨髓间充质干细胞占梗死后心脏功能的改善。
Mesenchymal stem cells (MSCs) have been recently demonstrated as a promising stem cell type to rescue damaged myocardium after acute infarction. One of the most important mechanisms underlying their therapeutic effects is the secretion of paracrine factors. However, the expression profile of paracrine factors of MSCs in infarcted hearts, especially at single cell level, is poorly defined. We aimed to depict the transcriptional profile of paracrine factors secreted by MSCs in vivo, with particular interest in the comparison between normal and infarcted hearts. Bone marrow mesenchymal stem cells were isolated and injected into mice hearts immediately after infarction surgery. Bioluminescence imaging (BLI) indicated a proportion of cells still alive even up to 10 days post surgery. Paralleled with survived cells, cardiac function was significantly improved after MSC injection compared to that in PBS-injected mice, indicated by MRI and histology. Despite increased number of vessels in MSC-injected hearts, endothelial cells and cardiomyocytes transdifferentiation were not observed in infarcted hearts 5 days after infarction. Furthermore, laser capture microdissection (LCM) followed by high through-put real time PCR was employed in our study, uncovering that the injected MSCs, compared to local cardiomyocytes, displayed elevated levels of secreted factors. To further investigate the regulation of those factors, we performed single cell analysis to dissect the gene expression profile of MSCs at single cell level in infarcted and normal hearts, respectively. Consistent with the in vivo observation, a similar regulation pattern of those factors was detected in cultured MSCs under hypoxia. Our study, for the first time, elucidated gene expression profiles, as well as regulation of paracrine factors, of MSCs at single cell level in vivo, indicating that paracrine factors from MSCs account for the improvement of cardiac function after infarction.
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影响因子：
24
作者：
Hare, Joshua M.;Traverse, Jay H.;Henry, Timothy D.;Dib, Nabil;Strumpf, Robert K.;Schulman, Steven P.;Gerstenblith, Gary;DeMaria, Anthony N.;Denktas, Ali E.;Gammon, Roger S.;Hermiller, James B., Jr.;Reisman, Mark A.;Schaer, Gary L.;Sherman, Warren
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Sherman, Warren
影响因子：
5.2
作者：
Wang, Xiaohong;Zhao, Tiemin;Huang, Wei;Wang, Tao;Qian, Jiang;Xu, Meifeng;Kranias, Evangelia G.;Wang, Yigang;Fan, Guo-Chang
通讯作者：
Fan, Guo-Chang
影响因子：
37.8
作者：
Jeevanantham V;Butler M;Saad A;Abdel-Latif A;Zuba-Surma EK;Dawn B
通讯作者：
Dawn B
影响因子：
20.1
作者：
Haider, Husnain Kh;Jiang, Shujia;Ashraf, Muhammad
通讯作者：
Ashraf, Muhammad
影响因子：
5
作者：
Fang, Jun;Chen, Lianglong;Wang, Weiwei
通讯作者：
Wang, Weiwei