The DOI matches its Crossref record; 4 of the 4 references it cites were found in a registry or an index.
Hypoxia-elicited mesenchymal stem cell-derived exosomes facilitates cardiac repair through miR-125b-mediated prevention of cell death in myocardial infarction
Open accessAbstract
Exosomes (Exo) secreted from hypoxia-conditioned bone marrow mesenchymal stem cells (BM-MSCs) were found to be protective for ischemic disease.However, the role of exosomal miRNA in the protective effect of hypoxia-conditioned BM-MSCs-derived Exo (Hypo-Exo) remains largely uncharacterized and the poor specificity of tissue targeting of Exo limits their clinical applications.Therefore, the objective of this study was to examine the effect of miRNA in Hypo-Exo on the repair of ischemic myocardium and its underlying mechanisms.We further developed modified Hypo-Exo with high specificity to the myocardium and evaluate its therapeutic effects.Methods: Murine BM-MSCs were subjected to hypoxia or normoxia culture and Exo were subsequently collected.Hypo-Exo or normoxia-conditioned BM-MSC-derived Exo (Nor-Exo) were administered to mice with permanent condition of myocardial infarction (MI).After 28 days, to evaluate the therapeutic effects of Hypo-Exo, infarction area and cardio output in Hypo-Exo and Nor-Exo treated MI mice were compared through Masson's trichrome staining and echocardiography respectively.We utilized the miRNA array to identify the significantly differentially expressed miRNAs between Nor-Exo and Hypo-Exo.One of the most enriched miRNA in Hypo-Exo was knockdown by applying antimiR in Hypoxia-conditioned BM-MSCs.Then we performed intramyocardial injection of candidate miRNA-knockdown-Hypo-Exo in a murine MI model, changes in the candidate miRNA's targets expression of cardiomyocytes and the cardiac function were characterized.We conjugated Hypo-Exo with an ischemic myocardium-targeted (IMT) peptide by bio-orthogonal chemistry, and tested its targeting specificity and therapeutic efficiency via systemic administration in the MI mice.Results: The miRNA array revealed significant enrichment of miR-125b-5p in Hypo-Exo compared with Nor-Exo.Administration of miR-125b knockdown Hypo-Exo significantly increased the infarction area and suppressed cardiomyocyte survival post-MI.Mechanistically, miR-125b knockdown Hypo-Exo lost the capability to suppress the expression of the proapoptotic genes p53 and BAK1 in cardiomyocytes.Intravenous administration of IMT-conjugated Hypo-Exo (IMT-Exo)Ivyspring
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Cites
Isolation and Characterization of Exosomes from Cell Culture Supernatants and Biological Fluids
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Cited by
Han, Y., Yang, J., Fang, J., Zhou, Y., Candi, E., Wang, J., Hua, D., Shao, C., & Shi, Y. (2022) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-022-00932-0 · Cited by 720
Self-citationMesenchymal 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
Roles and mechanisms of exosomal non-coding RNAs in human health and diseases
Li, C., Ni, Y.-Q., Xu, H., Xiang, Q.-Y., Zhao, Y., Zhan, J.-K., He, J.-Y., Li, S., & Liu, Y.-S. (2021) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-021-00779-x · Cited by 406
Self-citationBrennan, M. Á., Layrolle, P., & Mooney, D. J. (2020) · Advanced Functional Materials · doi:10.1002/adfm.201909125 · Cited by 396
Tsiapalis, D., & O’Driscoll, L. (2020) · Cells · doi:10.3390/cells9040991 · Cited by 313
Metadata
- Authors
- Zhu, L.-P., Tian, T., Wang, J.-Y., He, J.-N., Chen, T., Pan, M., Xu, L., Zhang, H.-X., Qiu, X.-T., Li, C.-C., Wang, K.-K., Shen, H., Zhang, G.-G., & Bai, Y.-P.
- Venue
- Theranostics
- Publisher
- Ivyspring International Publisher
- Published
- 2018
- Volume
- 8
- Issue
- 22
- Pages
- 6163-6177
- ISSN
- 1838-7640 (ISSN-L)
- OpenAlex
- W2903201035
- Cited by
- 545
- References
- 4
- FWCI
- 13.26
- Type
- journal article
- Language
- en
- Open access
- gold
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- Zhu, L.-P., Tian, T., Wang, J.-Y., He, J.-N., Chen, T., Pan, M., Xu, L., Zhang, H.-X., Qiu, X.-T., Li, C.-C., Wang, K.-K., Shen, H., Zhang, G.-G., & Bai, Y.-P. (2018). Hypoxia-elicited mesenchymal stem cell-derived exosomes facilitates cardiac repair through miR-125b-mediated prevention of cell death in myocardial infarction. Theranostics. https://doi.org/10.7150/thno.28021
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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