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Exosomes derived from human umbilical cord MSCs rejuvenate aged MSCs and enhance their functions for myocardial repair
Hong Yu
Corresponding Author
ORCiD: https://orcid.org/0000-0003-0521-8933
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This work is licensed under a CC BY 4.0 License. Read Full License
View the published version at Stem Cell Research & Therapy.
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 mycardiac 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, 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.
Keywords
Mesenchymal stem cells, exosomes, rejuvenation, microRNA, myocardial infarction
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CURRENT STATUS: Published
Version 2
Posted 08 Jun, 2020
Published
On 08 Jul, 2020
No community comments so far
Editorial decision: Accept
On 16 Jun, 2020
Review #1 received
Received 13 Jun, 2020
Reviewer #2 agreed
On 05 Jun, 2020
Review #2 received
Received 05 Jun, 2020
Reviewers invited
Invitations sent on 04 Jun, 2020
Reviewer #1 agreed
On 04 Jun, 2020
Editor assigned
On 31 May, 2020
Submission checks complete
On 30 May, 2020
Editor invited
On 30 May, 2020
No comments provided
Editorial decision: Major Revision
On 03 May, 2020
Review #2 received
Received 15 Apr, 2020
Reviewer #2 agreed
On 06 Apr, 2020
Review #1 received
Received 31 Mar, 2020
Reviewer #1 agreed
On 10 Mar, 2020
Reviewers invited
Invitations sent on 09 Mar, 2020
Editor assigned
On 18 Feb, 2020
Editor invited
On 17 Feb, 2020
Submission checks complete
On 17 Feb, 2020
First submitted
On 14 Feb, 2020
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
Subject Areas
Stem Cell & Developmental Cell Biology
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This preprint is under consideration at Stem Cell Research & Therapy. A preprint is a preliminary version of a manuscript that has not completed peer review at a journal. Research Square does not conduct peer review prior to posting preprints. The posting of a preprint on this server should not be interpreted as an endorsement of its validity or suitability for dissemination as established information or for guiding clinical practice.
Learn more about In Review
Research
Exosomes derived from human umbilical cord MSCs rejuvenate aged MSCs and enhance their functions for myocardial repair
Hong Yu
Corresponding Author
ORCiD: https://orcid.org/0000-0003-0521-8933
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
Peer Review Timeline
CURRENT STATUS: Published
Version 2
Posted 08 Jun, 2020
Published
On 08 Jul, 2020
No community comments so far
Editorial decision: Accept
On 16 Jun, 2020
Review #1 received
Received 13 Jun, 2020
Reviewer #2 agreed
On 05 Jun, 2020
Review #2 received
Received 05 Jun, 2020
Reviewers invited
Invitations sent on 04 Jun, 2020
Reviewer #1 agreed
On 04 Jun, 2020
Editor assigned
On 31 May, 2020
Submission checks complete
On 30 May, 2020
Editor invited
On 30 May, 2020
No comments provided
Editorial decision: Major Revision
On 03 May, 2020
Review #2 received
Received 15 Apr, 2020
Reviewer #2 agreed
On 06 Apr, 2020
Review #1 received
Received 31 Mar, 2020
Reviewer #1 agreed
On 10 Mar, 2020
Reviewers invited
Invitations sent on 09 Mar, 2020
Editor assigned
On 18 Feb, 2020
Editor invited
On 17 Feb, 2020
Submission checks complete
On 17 Feb, 2020
First submitted
On 14 Feb, 2020
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
Subject Areas
Stem Cell & Developmental Cell Biology
License:
This work is licensed under a CC BY 4.0 License. Read Full License
View the published version at Stem Cell Research & Therapy.
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 mycardiac 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, 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.
Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6