Exosomes Derived from Bone Marrow Mesenchymal Stem Cells Promote Angiogenesis in Ischemic Stroke Mice via Upregulation of MiR-21-5p.
Exosomes Derived from Bone Marrow Mesenchymal Stem Cells Promote Angiogenesis in Ischemic Stroke Mice via Upregulation of MiR-21-5p.
复制标题
骨髓间充质干细胞衍生的外泌体通过上调 MiR-21-5p 促进缺血性中风小鼠的血管生成。
DOI：
10.3390/biom12070883
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发表时间：
2022-06-24
期刊：
影响因子：
5.5
通讯作者：
中科院分区：
文献类型：
--
作者：
源自骨髓间充质干细胞的外泌体（BMSC - Exos）是骨髓间充质干细胞产生治疗效果的主要因素之一。本研究旨在探讨BMSC - Exos是否可通过miR - 21 - 5p促进缺血性脑卒中小鼠的血管生成。在缺血性脑卒中小鼠中，通过神经功能和梗死体积评估BMSC - Exos的治疗效果。通过BrdU/vWF免疫荧光染色检测微血管密度。在体外实验中，通过人脐静脉内皮细胞（HUVECs）的增殖、迁移和管形成来评估BMSC - Exos的促血管生成作用。使用Lipofectamine 2000将miR - 21 - 5p抑制剂转染到骨髓间充质干细胞中。通过qRT - PCR检测miR - 21 - 5p的表达。通过蛋白质印迹法测定VEGF、VEGFR2、Ang - 1和Tie - 2的表达水平。BMSC - Exos显著改善了脑缺血后的神经功能，减少了梗死体积，上调了微血管密度和miR - 21 - 5p的表达。体外实验表明，BMSC - Exos增强了HUVECs的功能，包括增殖、迁移和管形成。BMSC - Exos提高了VEGF、VEGFR2、Ang - 1和Tie - 2的表达水平。然而，miR - 21 - 5p抑制剂逆转了BMSC - Exos对HUVECs的促血管生成作用。这些结果表明，BMSC - Exos可通过上调miR - 21 - 5p促进血管生成，使其成为一种有吸引力的脑卒中恢复治疗策略。
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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影响因子：
5.9
作者：
Nalamolu KR;Chelluboina B;Fornal CA;Challa SR;Pinson DM;Wang DZ;Klopfenstein JD;Veeravalli KK
通讯作者：
Veeravalli KK
影响因子：
16.2
作者：
Cho C;Smallwood PM;Nathans J
通讯作者：
Nathans J
影响因子：
8.3
作者：
BEDERSON, JB;PITTS, LH;BARTKOWSKI, H
通讯作者：
BARTKOWSKI, H
影响因子：
6
作者：
Doeppner, Thorsten R.;Herz, Josephine;Hermann, Dirk M.
通讯作者：
Hermann, Dirk M.
影响因子：
5.3
作者：
Lu Y;Wen H;Huang J;Liao P;Liao H;Tu J;Zeng Y
通讯作者：
Zeng Y