Systemic Mesenchymal Stem Cell-Derived Exosomes Reduce Myocardial Infarct Size: Characterization With MRI in a Porcine Model.
Systemic Mesenchymal Stem Cell-Derived Exosomes Reduce Myocardial Infarct Size: Characterization With MRI in a Porcine Model.
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DOI：
10.3389/fcvm.2020.601990
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发表时间：
2020
影响因子：
3.6
通讯作者：
Richards AM
中科院分区：
文献类型：
--
作者：
Charles CJ;Li RR;Yeung T;Mazlan SMI;Lai RC;de Kleijn DPV;Lim SK;Richards AM
间充质干细胞(MSCs)通过其分泌体发挥心脏保护和修复作用，其活性成分(S)被鉴定为外切体，这支持了我们通过方便的静脉(IV)团注方法全身注射MSC外切体在猪心肌梗死(MI)模型中的有效性测试。结果表明，静脉注射外切体7天后，尽管hs肌钙蛋白T的释放几乎相同，但在心肌梗死后7天和28天测量的梗死区面积明显缩小(30-40%)，同时，外切体治疗减少了梗死区的透壁性，减少了梗死区的室壁变薄。与对照组相比，外切体处理的猪表现出相对保留的左心功能，并显著改善了部分室壁增厚的跌倒。然而，外切体治疗对整体左心功能的保护作用较小。心肌纤维化的增加可能削弱了整体左心功能的更大程度的保存，因为外体猪的T1值与对照组相比显著增加，尤其是在与梗塞相关的节段。综上所述，这些结果表明，与对照组相比，静脉注射外切体7天以上可以在相对保留心功能的情况下缩小梗死面积。
The observations that mesenchymal stem cells (MSCs) exert cardiac protection and repair via their secretome with the active component(s) identified as exosomes underpinned our test of the efficacy of MSC exosomes in a porcine model of myocardial infarction (MI) when administered systemically by the convenient method of intravenous (IV) bolus injection. Results show that 7 days of IV exosomes results in clear reduction (30–40%) of infarct size measured at both 7 and 28 days post-MI, despite near identical release of hs Troponin T. Together with reduced infarct size, exosome treatment reduced transmurality and lessened wall thinning in the infarct zone. Exosome treated pigs showed relative preservation of LV function with significant amelioration of falls in fractional wall thickening compared with control. However, global measures of LV function were less protected by exosome treatment. It is possible that greater preservation of global LV function may have been attenuated by increased cardiac fibrosis, as T1 values showed significant increase in the exosome pigs compared to control particularly in the infarct related segments. Taken together, these results show clear effects of IV exosomes administered over 7 days to reduce infarct size with relatively preserved cardiac function compared to control treated infarct pigs.
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