Electrical Stimulation Increases the Secretion of Cardioprotective Extracellular Vesicles from Cardiac Mesenchymal Stem Cells.
Electrical Stimulation Increases the Secretion of Cardioprotective Extracellular Vesicles from Cardiac Mesenchymal Stem Cells.
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作者：
临床试验表明，电刺激（ELSM）使用心脏再同步化治疗（CRT）或心脏收缩性调节（CCM）方法是治疗中重度心力衰竭患者的有效方法，但其机制尚不完全清楚。据报道，由心脏间充质干细胞（C-MSC）产生的细胞外囊泡（EV）通过细胞间通讯具有心脏保护作用。在这项研究中，我们研究了ELSM刺激对C-MSCs （C-MSCELSM）分泌EV的影响。我们观察到，与非刺激对照C-MSC （C-MSCCtrl）相比，来自C-MSCELSM的条件培养基（CM）赋予ev依赖性心脏保护作用增强。为了研究elsm刺激EV分泌的机制，我们检测了中性鞘磷脂酶2 （nSMase2）的蛋白水平，nSMase2是EV生物合成所需的内体分选复合体的关键酶。与C-MSCCtrl相比，我们检测到C-MSCELSM中nSMase2蛋白水平的时间依赖性增加。通过siRNA敲低C-MSC中的nSMase2可显著降低C-MSCELSM中EV的分泌，并减弱C-MSCELSM中CM对HL-1细胞的心脏保护作用。综上所述，我们的研究结果表明，elsm介导的C-MSC中EV分泌的增加通过涉及nSMase2的EV依赖机制增强了C-MSC的心脏保护作用。
Clinical trials have shown that electric stimulation (ELSM) using either cardiac resynchronization therapy (CRT) or cardiac contractility modulation (CCM) approaches is an effective treatment for patients with moderate to severe heart failure, but the mechanisms are incompletely understood. Extracellular vesicles (EV) produced by cardiac mesenchymal stem cells (C-MSC) have been reported to be cardioprotective through cell-to-cell communication. In this study, we investigated the effects of ELSM stimulation on EV secretion from C-MSCs (C-MSCELSM). We observed enhanced EV-dependent cardioprotection conferred by conditioned medium (CM) from C-MSCELSM compared to that from non-stimulated control C-MSC (C-MSCCtrl). To investigate the mechanisms of ELSM-stimulated EV secretion, we examined the protein levels of neutral sphingomyelinase 2 (nSMase2), a key enzyme of the endosomal sorting complex required for EV biosynthesis. We detected a time-dependent increase in nSMase2 protein levels in C-MSCELSM compared to C-MSCCtrl. Knockdown of nSMase2 in C-MSC by siRNA significantly reduced EV secretion in C-MSCELSM and attenuated the cardioprotective effect of CM from C-MSCELSM in HL-1 cells. Taken together, our results suggest that ELSM-mediated increases in EV secretion from C-MSC enhance the cardioprotective effects of C-MSC through an EV-dependent mechanism involving nSMase2.
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细胞外囊泡以及系统生物学和计算建模在心脏修复中的应用。
影响因子：
20.1
作者：
Garikipati VNS;Shoja-Taheri F;Davis ME;Kishore R
通讯作者：
Kishore R
DOI：
10.1126/science.aau6977
发表时间：
2020-02-07
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Kalluri R;LeBleu VS
通讯作者：
LeBleu VS
电刺激增强雪旺细胞衍生的外泌体介导的神经细胞活性
影响因子：
4.6
作者：
Hu, Ming;Hong, Li;Chen, Qian
通讯作者：
Chen, Qian
影响因子：
25
作者：
Asai H;Ikezu S;Tsunoda S;Medalla M;Luebke J;Haydar T;Wolozin B;Butovsky O;Kügler S;Ikezu T
通讯作者：
Ikezu T
影响因子：
3.4
作者：
Ju C;Shen Y;Ma G;Liu Y;Cai J;Kim IM;Weintraub NL;Liu N;Tang Y
通讯作者：
Tang Y