Customized Loading of microRNA-126 to Small Extracellular Vesicle-Derived Vehicles Improves Cardiac Function after Myocardial Infarction.
Customized Loading of microRNA-126 to Small Extracellular Vesicle-Derived Vehicles Improves Cardiac Function after Myocardial Infarction.
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DOI：
10.1021/acsnano.3c01534
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发表时间：
2023-10-24
期刊：
影响因子：
17.1
通讯作者：
Davis, Michael E.
中科院分区：
文献类型：
--
作者：
Bheri, Sruti;Brown, Milton E.;Park, Hyun-Ji;Brazhkina, Olga;Takaesu, Felipe;Davis, Michael E.
关键词：
小细胞外小泡(SEV)在心肌梗死后基于细胞的心脏修复中具有广阔的应用前景。这些SEV将包括microRNAs(MiRs)在内的有效货物包裹在双层膜内，当给药到细胞时，双层膜有助于SEV的摄取。然而，尽管SEV疗法有效，但由于亲本细胞SEV释放的不一致性和货物包裹体的可变性，SEV疗法受到限制。具有人工双层膜的合成SEV模拟物允许货物控制，但在体内给药时稳定性差，清除速度快。在此，我们开发了一种使用电穿孔技术的SEV样载体(ELV)，以我们之前发表的工作为基础，并在体内外研究了携带促血管生成miR-126的电穿孔ELV对大鼠缺血再灌注模型的有效性。我们发现，电穿孔miR-126+ELV改善了2D培养的心脏内皮细胞的管状形成参数，并改善了超声心动图和组织学参数，当给药到大鼠缺血再灌注损伤的左心室时。这项工作强调了使用电穿孔ELV作为运送用于心脏修复的精选miR货物的载体的价值。
Small extracellular vesicles (sEVs) are promising for cell-based cardiac repair after myocardial infarction. These sEVs encapsulate potent cargo, including microRNAs (miRs), within a bilayer membrane that aids sEV uptake when administered to cells. However, despite their efficacy, sEV therapies are limited by inconsistencies in the sEV release from parent cells and variability in cargo encapsulation. Synthetic sEV mimics with artificial bilayer membranes allow for cargo control but suffer poor stability and rapid clearance when administered in vivo. Here, we developed an sEV-like vehicle (ELV) using an electroporation technique, building upon our previously published work, and investigated the potency of delivering electroporated ELVs with pro-angiogenic miR-126 both in vitro and in vivo to a rat model of ischemia–reperfusion. We show that electroporated miR-126+ ELVs improve tube formation parameters when administered to 2D cultures of cardiac endothelial cells and improve both echocardiographic and histological parameters when delivered to a rat left ventricle after ischemia reperfusion injury. This work emphasizes the value of using electroporated ELVs as vehicles for delivery of select miR cargo for cardiac repair.
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影响因子：
5.9
作者：
Aminzadeh MA;Rogers RG;Fournier M;Tobin RE;Guan X;Childers MK;Andres AM;Taylor DJ;Ibrahim A;Ding X;Torrente A;Goldhaber JM;Lewis M;Gottlieb RA;Victor RA;Marbán E
通讯作者：
Marbán E
用于定量小鼠心脏体内缺血再灌注损伤的精制方法。
DOI：
10.1152/ajpheart.00836.2009
发表时间：
2009-12
期刊：
American journal of physiology. Heart and circulatory physiology
影响因子：
--
作者：
Bohl S;Medway DJ;Schulz-Menger J;Schneider JE;Neubauer S;Lygate CA
通讯作者：
Lygate CA
影响因子：
14
作者：
Seshadri, Gokulakrishnan;Sy, Jay C.;Brown, Milton;Dikalov, Sergey;Yang, Stephen C.;Murthy, Niren;Davis, Michael E.
通讯作者：
Davis, Michael E.
影响因子：
168.9
作者：
Makkar, Raj R.;Smith, Rachel R.;Cheng, Ke;Malliaras, Konstantinos;Thomson, Louise E. J.;Berman, Daniel;Czer, Lawrence S. C.;Marban, Linda;Mendizabal, Adam;Johnston, Peter V.;Russell, Stuart D.;Schuleri, Karl H.;Lardo, Albert C.;Gerstenblith, Gary;Marban, Eduardo
通讯作者：
Marban, Eduardo
影响因子：
17.4
作者：
Gustafson HH;Holt-Casper D;Grainger DW;Ghandehari H
通讯作者：
Ghandehari H