Knockdown of deleterious miRNA in progenitor cell-derived small extracellular vesicles enhances tissue repair in myocardial infarction.
Knockdown of deleterious miRNA in progenitor cell-derived small extracellular vesicles enhances tissue repair in myocardial infarction.
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DOI：
10.1126/sciadv.abo4616
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发表时间：
2023-03-03
期刊：
影响因子：
13.6
通讯作者：
中科院分区：
文献类型：
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作者：
小细胞外囊泡（sEV）通过递送分子货物和介导细胞信号传导在心脏细胞治疗中发挥关键作用。在sEV货物分子类型中，微小RNA（miRNA）特别有效且高度异质。然而，并非sEV中的所有miRNA都是有益的。先前的两项使用计算建模的研究将miR-192- 5 p和miR-432- 5 p鉴定为在心脏功能和修复中潜在有害的。在这里，我们表明，敲除心脏c-kit+细胞（CPC）衍生的sEV中的miR-192- 5 p和miR-432- 5 p可以增强sEV在体外和大鼠心脏缺血再灌注体内模型中的治疗能力。miR-192- 5 p和miR-432- 5 p缺失的CPC-sEV通过减少纤维化和坏死性炎症反应增强心脏功能。miR-192- 5 p耗尽的CPC-sEV还增强间充质基质细胞样细胞动员。从sEV中敲除有害的miRNAs可能是治疗慢性心肌梗死的一种有前景的治疗策略。生物信息学鉴定了细胞来源的sEV中的特定有害miRNA，并且这些miRNA的消耗增强了心脏功能。
Small extracellular vesicles (sEVs) play a critical role in cardiac cell therapy by delivering molecular cargo and mediating cellular signaling. Among sEV cargo molecule types, microRNA (miRNA) is particularly potent and highly heterogeneous. However, not all miRNAs in sEV are beneficial. Two previous studies using computational modeling identified miR-192-5p and miR-432-5p as potentially deleterious in cardiac function and repair. Here, we show that knocking down miR-192-5p and miR-432-5p in cardiac c-kit+ cell (CPC)–derived sEVs enhances the therapeutic capabilities of sEVs in vitro and in a rat in vivo model of cardiac ischemia reperfusion. miR-192-5p– and miR-432-5p–depleted CPC-sEVs enhance cardiac function by reducing fibrosis and necrotic inflammatory responses. miR-192-5p–depleted CPC-sEVs also enhance mesenchymal stromal cell–like cell mobilization. Knocking down deleterious miRNAs from sEV could be a promising therapeutic strategy for treatment of chronic myocardial infarction. Bioinformatics identifies specific deleterious miRNAs in cell-derived sEVs and depletion of these miRNA enhance cardiac function.
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DOI：
10.1002/stem.3445
发表时间：
2021-12
期刊：
Stem cells (Dayton, Ohio)
影响因子：
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作者：
Park HJ;De Jesus Morales KJ;Bheri S;Kassouf BP;Davis ME
通讯作者：
Davis ME
影响因子：
120.7
作者：
Heldman, Alan W.;DiFede, Darcy L.;Fishman, Joel E.;Zambrano, Juan P.;Trachtenberg, Barry H.;Karantalis, Vasileios;Mushtaq, Muzammil;Williams, Adam R.;Suncion, Viky Y.;McNiece, Ian K.;Ghersin, Eduard;Soto, Victor;Lopera, Gustavo;Miki, Roberto;Willens, Howard;Hendel, Robert;Mitrani, Raul;Pattany, Pradip;Feigenbaum, Gary;Oskouei, Behzad;Byrnes, John;Lowery, Maureen H.;Sierra, Julio;Pujol, Mariesty V.;Delgado, Cindy;Gonzalez, Phillip J.;Rodriguez, Jose E.;Bagno, Luiza Lima;Rouy, Didier;Altman, Peter;Foo, Cheryl Wong Po;da Silva, Jose;Anderson, Erica;Schwarz, Richard;Mendizabal, Adam;Hare, Joshua M.
通讯作者：
Hare, Joshua M.
影响因子：
20.1
作者：
Kanelidis AJ;Premer C;Lopez J;Balkan W;Hare JM
通讯作者：
Hare JM
影响因子：
20.1
作者：
Karantalis V;DiFede DL;Gerstenblith G;Pham S;Symes J;Zambrano JP;Fishman J;Pattany P;McNiece I;Conte J;Schulman S;Wu K;Shah A;Breton E;Davis-Sproul J;Schwarz R;Feigenbaum G;Mushtaq M;Suncion VY;Lardo AC;Borrello I;Mendizabal A;Karas TZ;Byrnes J;Lowery M;Heldman AW;Hare JM
通讯作者：
Hare JM
DOI：
10.1007/978-1-4939-1047-2_4
发表时间：
2014-01-01
期刊：
Methods in molecular biology (Clifton, N.J.)
影响因子：
--
作者：
French, Kristin M;Davis, Michael E
通讯作者：
Davis, Michael E