Exosomes derived from human umbilical cord MSCs rejuvenate aged MSCs and enhance their functions for myocardial repair
Abstract Background Age and other cardiovascular risk factors have been reported to impair the activities of mesenchymal stem cells (MSCs), which will affect the efficacy of stem cell transplantation. The objective of the study is to investigate whether exosomes derived from human umbilical cord MSC...
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| Format: | Article |
| Language: | English |
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BMC
2020-07-01
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| Series: | Stem Cell Research & Therapy |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s13287-020-01782-9 |
| _version_ | 1819015973135450112 |
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| author | Ning Zhang Jinyun Zhu Qunchao Ma Yun Zhao Yingchao Wang Xinyang Hu Jinghai Chen Wei Zhu Zhongchao Han Hong Yu |
| author_facet | Ning Zhang Jinyun Zhu Qunchao Ma Yun Zhao Yingchao Wang Xinyang Hu Jinghai Chen Wei Zhu Zhongchao Han Hong Yu |
| author_sort | Ning Zhang |
| collection | DOAJ |
| description | Abstract Background Age and other cardiovascular risk factors have been reported to impair the activities of mesenchymal stem cells (MSCs), which will affect the efficacy of stem cell transplantation. The objective of the study is to investigate whether exosomes derived from human umbilical cord MSCs (UMSCs) could enhance the activities of bone marrow MSCs from old person (OMSCs), and improve their capacity for cardiac repair. Methods Exosomes extracted from conditioned medium of UMSCs were used to treat OMSCs to generate OMSCsExo. The key molecule in the exosomes that have potential to rejuvenate aged MSCs were screened, and the role of OMSC was tested in the mouse model of mycardial infarction (MI). Results We found the activity of senescence-associated β-galactosidase and the expression of aging-related factors such as p53, p21, and p16 were significantly higher in OMSCs than those in UMSCs. After treatment with UMSC exosomes, these senescence phenotypes of OMSCs were remarkably reduced. The proliferation, migration, differentiation, and anti-apoptotic and paracrine effect were increased in OMSCsExo. In vivo study, mice with cardiac infarction had significantly better cardiac function, less fibrosis, and more angiogenesis after they were injected with OMSCsExo as compared with those with OMSC. There was more miR-136 expression in UMSCs and OMSCsExo than in OMSCs. Upregulation of miR-136 by transfection of miR-136 mimic into OMSCs significantly attenuated the apoptosis and senescence of OMSCs. Apoptotic peptidase activating factor (Apaf1) was found to be the downstream gene that is negatively regulated by miR-136 via directly targeting at its 3′UTR. Conclusion Our data suggest that exosomes from young MSCs can improve activities of aged MSCs and enhance their function for myocardial repair by transferring exosomal miR-136 and downregulating Apaf1. |
| first_indexed | 2024-12-21T02:40:14Z |
| format | Article |
| id | doaj.art-3ecc41ed8e384820b7b6f9167812a4d0 |
| institution | Directory Open Access Journal |
| issn | 1757-6512 |
| language | English |
| last_indexed | 2024-12-21T02:40:14Z |
| publishDate | 2020-07-01 |
| publisher | BMC |
| record_format | Article |
| series | Stem Cell Research & Therapy |
| spelling | doaj.art-3ecc41ed8e384820b7b6f9167812a4d02022-12-21T19:18:42ZengBMCStem Cell Research & Therapy1757-65122020-07-0111111510.1186/s13287-020-01782-9Exosomes derived from human umbilical cord MSCs rejuvenate aged MSCs and enhance their functions for myocardial repairNing Zhang0Jinyun Zhu1Qunchao Ma2Yun Zhao3Yingchao Wang4Xinyang Hu5Jinghai Chen6Wei Zhu7Zhongchao Han8Hong Yu9Department of Cardiology, Second Affiliated Hospital, College of Medicine, Zhejiang UniversityDepartment of Cardiology, Second Affiliated Hospital, College of Medicine, Zhejiang UniversityDepartment of Cardiology, Second Affiliated Hospital, College of Medicine, Zhejiang UniversityDepartment of Cardiology, Second Affiliated Hospital, College of Medicine, Zhejiang UniversityDepartment of Cardiology, Second Affiliated Hospital, College of Medicine, Zhejiang UniversityDepartment of Cardiology, Second Affiliated Hospital, College of Medicine, Zhejiang UniversityDepartment of Cardiology, Second Affiliated Hospital, College of Medicine, Zhejiang UniversityDepartment of Cardiology, Second Affiliated Hospital, College of Medicine, Zhejiang UniversityBeijing Engineering Laboratory of Perinatal Stem Cells, Beijing Institute of Health and Stem Cells, Health & Biotech CoDepartment of Cardiology, Second Affiliated Hospital, College of Medicine, Zhejiang UniversityAbstract Background Age and other cardiovascular risk factors have been reported to impair the activities of mesenchymal stem cells (MSCs), which will affect the efficacy of stem cell transplantation. The objective of the study is to investigate whether exosomes derived from human umbilical cord MSCs (UMSCs) could enhance the activities of bone marrow MSCs from old person (OMSCs), and improve their capacity for cardiac repair. Methods Exosomes extracted from conditioned medium of UMSCs were used to treat OMSCs to generate OMSCsExo. The key molecule in the exosomes that have potential to rejuvenate aged MSCs were screened, and the role of OMSC was tested in the mouse model of mycardial infarction (MI). Results We found the activity of senescence-associated β-galactosidase and the expression of aging-related factors such as p53, p21, and p16 were significantly higher in OMSCs than those in UMSCs. After treatment with UMSC exosomes, these senescence phenotypes of OMSCs were remarkably reduced. The proliferation, migration, differentiation, and anti-apoptotic and paracrine effect were increased in OMSCsExo. In vivo study, mice with cardiac infarction had significantly better cardiac function, less fibrosis, and more angiogenesis after they were injected with OMSCsExo as compared with those with OMSC. There was more miR-136 expression in UMSCs and OMSCsExo than in OMSCs. Upregulation of miR-136 by transfection of miR-136 mimic into OMSCs significantly attenuated the apoptosis and senescence of OMSCs. Apoptotic peptidase activating factor (Apaf1) was found to be the downstream gene that is negatively regulated by miR-136 via directly targeting at its 3′UTR. Conclusion Our data suggest that exosomes from young MSCs can improve activities of aged MSCs and enhance their function for myocardial repair by transferring exosomal miR-136 and downregulating Apaf1.http://link.springer.com/article/10.1186/s13287-020-01782-9Mesenchymal stem cellsExosomesRejuvenationMicroRNAMyocardial infarction |
| spellingShingle | Ning Zhang Jinyun Zhu Qunchao Ma Yun Zhao Yingchao Wang Xinyang Hu Jinghai Chen Wei Zhu Zhongchao Han Hong Yu Exosomes derived from human umbilical cord MSCs rejuvenate aged MSCs and enhance their functions for myocardial repair Stem Cell Research & Therapy Mesenchymal stem cells Exosomes Rejuvenation MicroRNA Myocardial infarction |
| title | Exosomes derived from human umbilical cord MSCs rejuvenate aged MSCs and enhance their functions for myocardial repair |
| title_full | Exosomes derived from human umbilical cord MSCs rejuvenate aged MSCs and enhance their functions for myocardial repair |
| title_fullStr | Exosomes derived from human umbilical cord MSCs rejuvenate aged MSCs and enhance their functions for myocardial repair |
| title_full_unstemmed | Exosomes derived from human umbilical cord MSCs rejuvenate aged MSCs and enhance their functions for myocardial repair |
| title_short | Exosomes derived from human umbilical cord MSCs rejuvenate aged MSCs and enhance their functions for myocardial repair |
| title_sort | exosomes derived from human umbilical cord mscs rejuvenate aged mscs and enhance their functions for myocardial repair |
| topic | Mesenchymal stem cells Exosomes Rejuvenation MicroRNA Myocardial infarction |
| url | http://link.springer.com/article/10.1186/s13287-020-01782-9 |
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