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Fengxiang Zhang
The First Affiliated Hospital of Nanjing Medical University
Corresponding Author
ORCiD: https://orcid.org/0000-0003-0125-3926
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Background Exosome transplantation is a promising cell-free therapeutic approach for the treatment of ischemic heart disease. The purpose of this study was to explore whether exosomes derived from Macrophage migration inhibitory factor (MIF) engineered umbilical cord MSCs (ucMSCs) exhibit superior cardioprotective effects in a rat model of AMI and reveal the mechanisms underlying it.
Results Exosomes isolated from ucMSCs (MSC-Exo), MIF engineered ucMSCs (MIF-Exo) and MIF downregulated ucMSCs (siMIF-Exo) were used to investigate cellular protective function in human umbilical vein endothelial cells (HUVECs) and H9C2 cardiomyocytes under hypoxia and serum deprivation (H/SD) and infarcted hearts in rats. Compared with MSC-Exo and siMIF-Exo, MIF-Exo significantly enhanced proliferation, migration, and angiogenesis of HUVECs and inhibited H9C2 cardiomyocyte apoptosis under H/SD in vitro. MIF-Exo also significantly inhibited cardiomyocyte apoptosis, reduced fibrotic area, and improved cardiac function as measured by echocardiography in infarcted rats in vivo. Exosomal miRNAs sequencing and qRT-PCR confirmed miRNA-133a-3p significantly increased in MIF-Exo. The biological effects of HUVECs and H9C2 cardiomyocytes were attenuated with incubation of MIF-Exo and miR-133a-3p inhibitors. These effects were accentuated with incubation of siMIF-Exo and miR-133a-3p mimics that increased the phosphorylation of AKT protein in these cells.
Conclusion MIF-Exo can provide cardioprotective effects by promoting angiogenesis, inhibiting apoptosis, reducing fibrosis, and preserving heart function in vitro and in vivo. The mechanism in the biological activities of MIF-Exo involves miR-133a-3p and the downstream AKT signaling pathway.
Keywords
Exosomes, macrophage migration inhibitory factor, ucMSCs, miR-133a-3p, Myocardial infarction
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This is a list of supplementary files associated with this preprint. Click to download.
- SupplementarytablesandfiguresR1.pdf
Figure S1-S2 and Table S1-S3
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CURRENT STATUS: Published
View the published article at Journal of Nanobiotechnology.
Version 2
Posted 27 Jan, 2021
No community comments so far
Editorial decision: Accept
On 14 Feb, 2021
Review #2 received
Received 09 Feb, 2021
Reviewer #2 agreed
On 03 Feb, 2021
Reviewers invited
Invitations sent on 24 Jan, 2021
Reviewer #1 agreed
On 24 Jan, 2021
Review #1 received
Received 24 Jan, 2021
Editor assigned
On 21 Jan, 2021
Submission checks complete
On 21 Jan, 2021
Editor invited
On 21 Jan, 2021
No comments provided
Editorial decision: Major revision
On 22 Dec, 2020
Review #2 received
Received 21 Dec, 2020
Review #1 received
Received 11 Dec, 2020
Reviewer #2 agreed
On 02 Dec, 2020
Reviewers invited
Invitations sent on 29 Nov, 2020
Reviewer #1 agreed
On 29 Nov, 2020
Editor invited
On 27 Nov, 2020
Editor assigned
On 27 Nov, 2020
Submission checks complete
On 27 Nov, 2020
First submitted
On 24 Nov, 2020
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See the published version of this preprint at Journal of Nanobiotechnology.
This is a preprint, 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
Fengxiang Zhang
The First Affiliated Hospital of Nanjing Medical University
Corresponding Author
ORCiD: https://orcid.org/0000-0003-0125-3926
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
View the published article at Journal of Nanobiotechnology.
Version 2
Posted 27 Jan, 2021
No community comments so far
Editorial decision: Accept
On 14 Feb, 2021
Review #2 received
Received 09 Feb, 2021
Reviewer #2 agreed
On 03 Feb, 2021
Reviewers invited
Invitations sent on 24 Jan, 2021
Reviewer #1 agreed
On 24 Jan, 2021
Review #1 received
Received 24 Jan, 2021
Editor assigned
On 21 Jan, 2021
Submission checks complete
On 21 Jan, 2021
Editor invited
On 21 Jan, 2021
No comments provided
Editorial decision: Major revision
On 22 Dec, 2020
Review #2 received
Received 21 Dec, 2020
Review #1 received
Received 11 Dec, 2020
Reviewer #2 agreed
On 02 Dec, 2020
Reviewers invited
Invitations sent on 29 Nov, 2020
Reviewer #1 agreed
On 29 Nov, 2020
Editor invited
On 27 Nov, 2020
Editor assigned
On 27 Nov, 2020
Submission checks complete
On 27 Nov, 2020
First submitted
On 24 Nov, 2020
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
License:
This work is licensed under a CC BY 4.0 License. Read Full License
View the published article at Journal of Nanobiotechnology.
Background Exosome transplantation is a promising cell-free therapeutic approach for the treatment of ischemic heart disease. The purpose of this study was to explore whether exosomes derived from Macrophage migration inhibitory factor (MIF) engineered umbilical cord MSCs (ucMSCs) exhibit superior cardioprotective effects in a rat model of AMI and reveal the mechanisms underlying it.
Results Exosomes isolated from ucMSCs (MSC-Exo), MIF engineered ucMSCs (MIF-Exo) and MIF downregulated ucMSCs (siMIF-Exo) were used to investigate cellular protective function in human umbilical vein endothelial cells (HUVECs) and H9C2 cardiomyocytes under hypoxia and serum deprivation (H/SD) and infarcted hearts in rats. Compared with MSC-Exo and siMIF-Exo, MIF-Exo significantly enhanced proliferation, migration, and angiogenesis of HUVECs and inhibited H9C2 cardiomyocyte apoptosis under H/SD in vitro. MIF-Exo also significantly inhibited cardiomyocyte apoptosis, reduced fibrotic area, and improved cardiac function as measured by echocardiography in infarcted rats in vivo. Exosomal miRNAs sequencing and qRT-PCR confirmed miRNA-133a-3p significantly increased in MIF-Exo. The biological effects of HUVECs and H9C2 cardiomyocytes were attenuated with incubation of MIF-Exo and miR-133a-3p inhibitors. These effects were accentuated with incubation of siMIF-Exo and miR-133a-3p mimics that increased the phosphorylation of AKT protein in these cells.
Conclusion MIF-Exo can provide cardioprotective effects by promoting angiogenesis, inhibiting apoptosis, reducing fibrosis, and preserving heart function in vitro and in vivo. The mechanism in the biological activities of MIF-Exo involves miR-133a-3p and the downstream AKT signaling pathway.
Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6
Figure 7
Figure 8
This is a list of supplementary files associated with this preprint. Click to download.
- SupplementarytablesandfiguresR1.pdf
Figure S1-S2 and Table S1-S3
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