Exosomes Derived from Bone Marrow Mesenchymal Stem Cells Promote Angiogenesis in Ischemic Stroke Mice via Upregulation of MiR-21-5p

被引:45
|
作者
Hu, Hui [1 ]
Hu, Xiaowei [1 ]
Li, Lin [1 ]
Fang, Yan [1 ]
Yang, Yan [1 ]
Gu, Jingjing [2 ]
Xu, Jiadong [1 ]
Chu, Lisheng [1 ]
机构
[1] Zhejiang Chinese Med Univ, Dept Physiol, Hangzhou 310053, Peoples R China
[2] Zhejiang Chinese Med Univ, Dept Pathol, Hangzhou 310053, Peoples R China
基金
中国国家自然科学基金;
关键词
bone marrow mesenchymal stem cells; exosome; microRNA; angiogenesis; cerebral ischemia; STROMAL CELLS; NEUROGENESIS;
D O I
10.3390/biom12070883
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Exosomes derived from bone mesenchymal stem cells (BMSC-Exos) are one of the main factors responsible for the therapeutic effects of BMSCs. The study aimed to investigate whether BMSC-Exos could promote angiogenesis in ischemic stroke mice via miR-21-5p. In ischemic stroke mice, the therapeutic effects of BMSC-Exos were evaluated by neurological functions and infarct volume. Microvessel density was detected by BrdU/vWF immunofluorescence staining. In in vitro experiments, the proangiogenic effects of BMSC-Exos were assessed via proliferation, migration, and tube formation of human umbilical vein endothelial cells (HUVECs). The miR-21-5p inhibitor was transfected into BMSCs using Lipofectamine 2000. miR-21-5p expression was detected by qRT-PCR. The expression levels of VEGF, VEGFR2, Ang-1, and Tie-2 were determined by Western blot. BMSC-Exos significantly improved neurological functions and reduced infarct volume, upregulated microvessel density, and miR-21-5p expression after cerebral ischemia. In vitro assays revealed that BMSC-Exos enhanced HUVECs functions including proliferation, migration, and tube formation. BMSC-Exos increased the expression levels of VEGF, VEGFR2, Ang-1, and Tie-2. However, the proangiogenic effects of BMSC-Exos on HUVECs were reversed by the miR-21-5p inhibitor. These results suggest that BMSC-Exos could promote angiogenesis via miR-21-5p upregulation, making them an attractive treatment strategy for stroke recovery.
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页数:18
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