Exosomes from neuronal stem cells may protect the heart from ischaemia/reperfusion injury via JAK1/2 and gp130.
Exosomes from neuronal stem cells may protect the heart from ischaemia/reperfusion injury via JAK1/2 and gp130.
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DOI：
10.1111/jcmm.16515
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发表时间：
2021-05
影响因子：
5.3
通讯作者：
Davidson SM
中科院分区：
文献类型：
--
作者：
Katsur M;He Z;Vinokur V;Corteling R;Yellon DM;Davidson SM
心肌梗塞需要紧急再灌注以挽救存活的心脏组织。然而，再灌注通过促进心肌细胞线粒体损伤进一步增加梗死面积。来自各种不同细胞来源的外泌体已被证明可以激活心肌细胞中的心脏保护途径，从而减少梗死面积。然而，目前很难获得足够数量的高纯度外泌体用于临床研究。为了克服这一问题，我们使用了从CTX0E03神经干细胞中分离的外泌体，这种外泌体具有遗传稳定性，条件诱导性，可以在工业规模上生产。然而，来自神经干细胞的外泌体是否可以减少心脏缺血/再灌注损伤尚不清楚。在这项研究中，我们证明来自分化的CTX0E03细胞的外泌体可以减少小鼠梗死面积。在体外实验中，这些外泌体延迟心肌细胞线粒体通透性过渡孔打开，这是心肌细胞再灌注后死亡的原因。MPTP抑制的机制是通过gp130信号通路和下游的JAK/STAT通路。我们的结果支持先前的发现，即来自非心肌细胞相关细胞的外泌体产生能够保护心肌细胞免受心肌梗死的外泌体。我们预计我们的发现可能会鼓励科学家使用从可重复的临床级细胞库中获得的外泌体进行缺血/再灌注研究。
Myocardial infarction requires urgent reperfusion to salvage viable heart tissue. However, reperfusion increases infarct size further by promoting mitochondrial damage in cardiomyocytes. Exosomes from a wide range of different cell sources have been shown to activate cardioprotective pathways in cardiomyocytes, thereby reducing infarct size. Yet, it is currently challenging to obtain highly pure exosomes in quantities enough for clinical studies. To overcome this problem, we used exosomes isolated from CTX0E03 neuronal stem cells, which are genetically stable, conditionally inducible and can be produced on an industrial scale. However, it is unknown whether exosomes from neuronal stem cells may reduce cardiac ischaemia/reperfusion injury. In this study, we demonstrate that exosomes from differentiating CTX0E03 cells can reduce infarct size in mice. In an in vitro assay, these exosomes delayed cardiomyocyte mitochondrial permeability transition pore opening, which is responsible for cardiomyocyte death after reperfusion. The mechanism of MPTP inhibition was via gp130 signalling and the downstream JAK/STAT pathway. Our results support previous findings that exosomes from non‐cardiomyocyte‐related cells produce exosomes capable of protecting cardiomyocytes from myocardial infarction. We anticipate our findings may encourage scientists to use exosomes obtained from reproducible clinical‐grade stocks of cells for their ischaemia/reperfusion studies.
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DOI：
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发表时间：
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影响因子：
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