Exosomes from human urine-derived stem cells enhanced neurogenesis via miR-26a/HDAC6 axis after ischaemic stroke

Exosomes from human urine-derived stem cells enhanced neurogenesis via miR-26a/HDAC6 axis after ischaemic stroke
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来自人尿干细胞的外泌体通过 miR-26a/HDAC6 轴增强缺血性中风后的神经发生

DOI:
10.1111/jcmm.14774
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发表时间:
2020-01-01
影响因子:
5.3
通讯作者:
Deng, Zhifeng
Deng, Zhifeng
中科院分区:
医学2区
文献类型:
--
作者:
Ling, Xiaozheng;Zhang, Guowei;Deng, Zhifeng

文献摘要

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内源性神经发生为缺血性卒中后的脑修复和长期功能恢复提供了希望。然而,来自人尿源性干细胞(USC-Exos)的外泌体在神经发生中的作用仍不清楚。本研究旨在研究USC-Exos是否增强脑缺血的神经发生并促进功能恢复。通过使用实验性中风大鼠模型,我们发现静脉注射USC-Exos增强了缺血性中风后大鼠的神经发生并减轻了神经功能缺损。我们使用神经干细胞(NSCs)进行氧-糖剥夺/复氧(OGD/R)作为缺血性脑卒中的体外模型。体外实验结果表明,USC-Exos能促进OGD/R后神经干细胞的增殖和向神经元分化。值得注意的是,进一步的机制研究表明,USC-Exos的促神经发生作用可能部分归因于通过转移外泌体微小RNA-26 a(miR-26 a)来抑制组蛋白脱乙酰酶6(HDAC 6)。总而言之,这项研究表明USC-Exos可以作为治疗脑缺血的一种新的有前途的策略,这凸显了USC-Exos的应用。
Endogenous neurogenesis holds promise for brain repair and long-term functional recovery after ischaemic stroke. However, the effects of exosomes from human urine-derived stem cells (USC-Exos) in neurogenesis remain unclear. This study aimed to investigate whether USC-Exos enhanced neurogenesis and promoted functional recovery in brain ischaemia. By using an experimental stroke rat model, we found that intravenous injection of USC-Exos enhanced neurogenesis and alleviated neurological deficits in post-ischaemic stroke rats. We used neural stem cells (NSCs) subjected to oxygen-glucose deprivation/reoxygenation (OGD/R) as an in vitro model of ischaemic stroke. The in vitro results suggested that USC-Exos promoted both proliferation and neuronal differentiation of NSCs after OGD/R. Notably, a further mechanism study revealed that the pro-neurogenesis effects of USC-Exos may be partially attributed to histone deacetylase 6 (HDAC6) inhibition via the transfer of exosomal microRNA-26a (miR-26a). Taken together, this study indicates that USC-Exos can be used as a novel promising strategy for brain ischaemia, which highlights the application of USC-Exos.