The DOI matches its Crossref record; 38 of the 38 references it cites were found in a registry or an index.
Mesenchymal stromal cell-derived exosomes attenuate myocardial ischaemia-reperfusion injury through miR-182-regulated macrophage polarization
Open accessAbstract
AIMS: Mesenchymal stromal cells (MSCs) gradually become attractive candidates for cardiac inflammation modulation, yet understanding of the mechanism remains elusive. Strikingly, recent studies indicated that exosomes secreted by MSCs might be a novel mechanism for the beneficial effect of MSCs transplantation after myocardial infarction. We therefore explored the role of MSC-derived exosomes (MSC-Exo) in the immunomodulation of macrophages after myocardial ischaemia/reperfusion (I/R) and its implications in cardiac injury repair. METHODS AND RESULTS: Exosomes were isolated from the supernatant of MSCs using gradient centrifugation method. Administration of MSC-Exo to mice through intramyocardial injection after myocardial I/R reduced infarct size and alleviated inflammation level in heart and serum. Systemic depletion of macrophages with clodronate liposomes abolished the curative effects of MSC-Exo. MSC-Exo modified the polarization of M1 macrophages to M2 macrophages both in vivo and in vitro. miRNA sequencing of MSC-Exo and bioinformatics analysis implicated miR-182 as a potent candidate mediator of macrophage polarization and toll-like receptor 4 (TLR4) as a downstream target. Diminishing miR-182 in MSC-Exo partially attenuated its modulation of macrophage polarization. Likewise, knock down of TLR4 also conferred cardioprotective efficacy and reduced inflammation level in a mouse model of myocardial I/R. CONCLUSION: Our data indicate that MSC-Exo attenuates myocardial I/R injury in mice via shuttling miR-182 that modifies the polarization status of macrophages. This study sheds new light on the application of MSC-Exo as a potential therapeutic tool for myocardial I/R injury.
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Cites
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Harnessing the Mesenchymal Stem Cell Secretome for the Treatment of Cardiovascular Disease
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Cited by
Signaling pathways and targeted therapy for myocardial infarction
Zhang, Q., Wang, L., Wang, S., Cheng, H., Xu, L., Pei, G., Wang, Y., Fu, C., Jiang, Y., He, C., et al. (2022) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-022-00925-z · Cited by 831
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Mesenchymal Stem Cell-Derived Exosomes: Applications in Regenerative Medicine
Hade, M. D., Suire, C. N., & Suo, Z. (2021) · Cells · doi:10.3390/cells10081959 · Cited by 607
Liu, W., Rong, Y., Wang, J., Zhou, Z., Ge, X., Ji, C., Jiang, D., Gong, F., Li, L., Chen, J., et al. (2020) · Journal of Neuroinflammation · doi:10.1186/s12974-020-1726-7 · Cited by 573
Arabpour, M., Saghazadeh, A., & Rezaei, N. (2021) · International Immunopharmacology · doi:10.1016/j.intimp.2021.107823 · Cited by 511
Metadata
- Authors
- Zhao, J., Li, X., Hu, J., Chen, F., Qiao, S., Sun, X., Gao, L., Xie, J., & Xu, B.
- Venue
- Cardiovascular Research
- Publisher
- Oxford University Press (OUP)
- Published
- 2019-02-08
- Volume
- 115
- Issue
- 7
- Pages
- 1205-1216
- ISSN
- 0008-6363 (ISSN-L)
- 1755-3245
- OpenAlex
- W2912418307
- Cited by
- 769
- References
- 38
- FWCI
- 24.06
- Type
- journal article
- Language
- en
- Open access
- hybrid
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- Zhao, J., Li, X., Hu, J., Chen, F., Qiao, S., Sun, X., Gao, L., Xie, J., & Xu, B. (2019). Mesenchymal stromal cell-derived exosomes attenuate myocardial ischaemia-reperfusion injury through miR-182-regulated macrophage polarization. Cardiovascular Research. https://doi.org/10.1093/cvr/cvz040
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