Hypoxia-challenged MSC-derived exosomes deliver miR-210 to attenuate post-infarction cardiac apoptosis
Abstract Background Myocardial infarction (MI) is a major cause of death worldwide. Although percutaneous coronary intervention and coronary artery bypass grafting can prolong life, cardiac damage persists. In particular, cardiomyocytes have no regenerative capacity. Mesenchymal stem cells (MSCs) ar...
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| Format: | Article |
| Language: | English |
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BMC
2020-06-01
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| Series: | Stem Cell Research & Therapy |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s13287-020-01737-0 |
| _version_ | 1828768675334717440 |
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| author | Hao Cheng Shufu Chang Rende Xu Lu Chen Xiaoyue Song Jian Wu Juying Qian Yunzeng Zou Jianying Ma |
| author_facet | Hao Cheng Shufu Chang Rende Xu Lu Chen Xiaoyue Song Jian Wu Juying Qian Yunzeng Zou Jianying Ma |
| author_sort | Hao Cheng |
| collection | DOAJ |
| description | Abstract Background Myocardial infarction (MI) is a major cause of death worldwide. Although percutaneous coronary intervention and coronary artery bypass grafting can prolong life, cardiac damage persists. In particular, cardiomyocytes have no regenerative capacity. Mesenchymal stem cells (MSCs) are attractive candidates for the treatment of MI. The manner by which MSCs exert a beneficial effect upon injured cells is a source of continued study. Methods After the isolation and identification of exosomes from MSCs, the expression of miR-210 was determined by microarray chip. Subsequently, gain- and loss-function approaches were conducted to detect the role of exosomes and exosomal-miR-210 in cell proliferation and apoptosis of cardiomyocytes, as well as the MI in vivo. Dual-Luciferase Report Gene System was used to demonstrate the target gene of miR-210. Results We tested the hypothesis that MSC-derived exosomes transfer specific miRNA to protect cardiomyocytes from apoptotic cell death. Interestingly, direct cardiac injection of MSC exosomes reduced infarct size and improved heart function after coronary ligation. In vitro, the MSC exosomes enhanced cardiomyocyte survival to hypoxia. Confirmation of exosome uptake in myocytes was confirmed. Dual-luciferase reporter assay implicated miR-210 as a mediator of the therapeutic effect and AIFM3 as a downstream target. Treatment with miR-210 overexpressing MSC exosomes improved myocyte protection to both in vitro and in vivo stress. Furthermore, the endogenous and exogenous miR-210 had the same therapeutic effects. Conclusion These results demonstrated that the beneficial effects offered by MSC-exosomes transplantation after MI are at least partially because of excreted exosome containing mainly miR-210. Graphical abstract |
| first_indexed | 2024-12-11T13:34:05Z |
| format | Article |
| id | doaj.art-f257b5dff21e467cbf58a262bbee4d94 |
| institution | Directory Open Access Journal |
| issn | 1757-6512 |
| language | English |
| last_indexed | 2024-12-11T13:34:05Z |
| publishDate | 2020-06-01 |
| publisher | BMC |
| record_format | Article |
| series | Stem Cell Research & Therapy |
| spelling | doaj.art-f257b5dff21e467cbf58a262bbee4d942022-12-22T01:05:09ZengBMCStem Cell Research & Therapy1757-65122020-06-0111111410.1186/s13287-020-01737-0Hypoxia-challenged MSC-derived exosomes deliver miR-210 to attenuate post-infarction cardiac apoptosisHao Cheng0Shufu Chang1Rende Xu2Lu Chen3Xiaoyue Song4Jian Wu5Juying Qian6Yunzeng Zou7Jianying Ma8Department of Cardiology, Zhongshan Hospital, Fudan UniversityDepartment of Cardiology, Zhongshan Hospital, Fudan UniversityDepartment of Cardiology, Zhongshan Hospital, Fudan UniversityDepartment of Cardiology, Zhongshan Hospital, Fudan UniversityDepartment of Cardiology, Zhongshan Hospital, Fudan UniversityShanghai Institute of Cardiovascular Diseases, Zhongshan Hospital and Institute of Biomedical Sciences, Fudan UniversityDepartment of Cardiology, Zhongshan Hospital, Fudan UniversityShanghai Institute of Cardiovascular Diseases, Zhongshan Hospital and Institute of Biomedical Sciences, Fudan UniversityDepartment of Cardiology, Zhongshan Hospital, Fudan UniversityAbstract Background Myocardial infarction (MI) is a major cause of death worldwide. Although percutaneous coronary intervention and coronary artery bypass grafting can prolong life, cardiac damage persists. In particular, cardiomyocytes have no regenerative capacity. Mesenchymal stem cells (MSCs) are attractive candidates for the treatment of MI. The manner by which MSCs exert a beneficial effect upon injured cells is a source of continued study. Methods After the isolation and identification of exosomes from MSCs, the expression of miR-210 was determined by microarray chip. Subsequently, gain- and loss-function approaches were conducted to detect the role of exosomes and exosomal-miR-210 in cell proliferation and apoptosis of cardiomyocytes, as well as the MI in vivo. Dual-Luciferase Report Gene System was used to demonstrate the target gene of miR-210. Results We tested the hypothesis that MSC-derived exosomes transfer specific miRNA to protect cardiomyocytes from apoptotic cell death. Interestingly, direct cardiac injection of MSC exosomes reduced infarct size and improved heart function after coronary ligation. In vitro, the MSC exosomes enhanced cardiomyocyte survival to hypoxia. Confirmation of exosome uptake in myocytes was confirmed. Dual-luciferase reporter assay implicated miR-210 as a mediator of the therapeutic effect and AIFM3 as a downstream target. Treatment with miR-210 overexpressing MSC exosomes improved myocyte protection to both in vitro and in vivo stress. Furthermore, the endogenous and exogenous miR-210 had the same therapeutic effects. Conclusion These results demonstrated that the beneficial effects offered by MSC-exosomes transplantation after MI are at least partially because of excreted exosome containing mainly miR-210. Graphical abstracthttp://link.springer.com/article/10.1186/s13287-020-01737-0Myocardial infarctionExosomeMesenchymal stem cellsHypoxiaApoptosis |
| spellingShingle | Hao Cheng Shufu Chang Rende Xu Lu Chen Xiaoyue Song Jian Wu Juying Qian Yunzeng Zou Jianying Ma Hypoxia-challenged MSC-derived exosomes deliver miR-210 to attenuate post-infarction cardiac apoptosis Stem Cell Research & Therapy Myocardial infarction Exosome Mesenchymal stem cells Hypoxia Apoptosis |
| title | Hypoxia-challenged MSC-derived exosomes deliver miR-210 to attenuate post-infarction cardiac apoptosis |
| title_full | Hypoxia-challenged MSC-derived exosomes deliver miR-210 to attenuate post-infarction cardiac apoptosis |
| title_fullStr | Hypoxia-challenged MSC-derived exosomes deliver miR-210 to attenuate post-infarction cardiac apoptosis |
| title_full_unstemmed | Hypoxia-challenged MSC-derived exosomes deliver miR-210 to attenuate post-infarction cardiac apoptosis |
| title_short | Hypoxia-challenged MSC-derived exosomes deliver miR-210 to attenuate post-infarction cardiac apoptosis |
| title_sort | hypoxia challenged msc derived exosomes deliver mir 210 to attenuate post infarction cardiac apoptosis |
| topic | Myocardial infarction Exosome Mesenchymal stem cells Hypoxia Apoptosis |
| url | http://link.springer.com/article/10.1186/s13287-020-01737-0 |
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