The DOI matches its Crossref record; 65 of the 65 references it cites were found in a registry or an index.
Exosomal miR-146a Contributes to the Enhanced Therapeutic Efficacy of Interleukin-1β-Primed Mesenchymal Stem Cells Against Sepsis
Open accessAbstract
Improving the immunomodulatory efficacy of mesenchymal stem cells (MSCs) through pretreatment with pro-inflammatory cytokines is an evolving field of investigation. However, the underlying mechanisms have not been fully clarified. Here, we pretreated human umbilical cord-derived MSCs with interleukin-1β (IL-1β) and evaluated their therapeutic effects in a cecal ligation and puncture-induced sepsis model. We found that systemic administration of IL-1β-pretreated MSCs (βMSCs) ameliorated the symptoms of murine sepsis more effectively and increased the survival rate compared with naïve MSCs. Furthermore, βMSCs could more effectively induce macrophage polarization toward an anti-inflammatory M2 phenotype through the paracrine activity. Mechanistically, we demonstrated that βMSC-derived exosomes contributed to the enhanced immunomodulatory properties of βMSCs both in vitro and in vivo. Importantly, we found that miR-146a, a well-known anti-inflammatory microRNA, was strongly upregulated by IL-1β stimulation and selectively packaged into exosomes. This exosomal miR-146a was transferred to macrophages, resulted in M2 polarization, and finally led to increased survival in septic mice. In contrast, inhibition of miR-146a through transfection with miR-146a inhibitors partially negated the immunomodulatory properties of βMSC-derived exosomes. Taken together, IL-1β pretreatment effectively enhanced the immunomodulatory properties of MSCs partially through exosome-mediated transfer of miR-146a. Therefore, we believe that IL-1β pretreatment may provide a new modality for better therapeutic application of MSCs in inflammatory disorders.
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1 retracted
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Ceramide Triggers Budding of Exosome Vesicles into Multivesicular Endosomes
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Cited by
Ren, J., Ding, L., Zhang, D., Shi, G., Xu, Q., Shen, S., Wang, Y., Wang, T., & Hou, Y. (2018) · Theranostics · doi:10.7150/thno.25541 · Cited by 698
Self-citationStem Cell-Derived Exosomes as Nanotherapeutics for Autoimmune and Neurodegenerative Disorders
Riazifar, M., Mohammadi, M. R., Pone, E. J., Yeri, A., Lässer, C., Segaliny, A. I., McIntyre, L. L., Shelke, G. V., Hutchins, E., Hamamoto, A., et al. (2019) · ACS Nano · doi:10.1021/acsnano.9b01004 · Cited by 551
MSC exosome works through a protein-based mechanism of action
Toh, W. S., Lai, R. C., Zhang, B., & Lim, S. K. (2018) · Biochemical Society Transactions · doi:10.1042/bst20180079 · Cited by 394
Ren, W., Hou, J., Yang, C., Wang, H., Wu, S., Wu, Y., Zhao, X., & Lu, C. (2019) · Journal of Experimental & Clinical Cancer Research · doi:10.1186/s13046-019-1027-0 · Cited by 341
Self-citationSun, G., Li, G., Li, D., Huang, W., Zhang, R., Zhang, H., Duan, Y., & Wang, B. (2018) · Materials Science and Engineering C · doi:10.1016/j.msec.2018.04.006 · Cited by 314
Metadata
- Authors
- Song, Y., Dou, H., Li, X., Zhao, X., Li, Y., Liu, D., Ji, J., Liu, F., Ding, L., Ni, Y., & Hou, Y.
- Venue
- Stem Cells
- Publisher
- Oxford University Press (OUP)
- Published
- 2017-02-05
- Volume
- 35
- Issue
- 5
- Pages
- 1208-1221
- ISSN
- 1066-5099 (ISSN-L)
- 1549-4918
- OpenAlex
- W2572058121
- Cited by
- 482
- References
- 65
- FWCI
- 19.40
- Type
- journal article
- Language
- en
- Open access
- hybrid
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- Song, Y., Dou, H., Li, X., Zhao, X., Li, Y., Liu, D., Ji, J., Liu, F., Ding, L., Ni, Y., & Hou, Y. (2017). Exosomal miR-146a Contributes to the Enhanced Therapeutic Efficacy of Interleukin-1β-Primed Mesenchymal Stem Cells Against Sepsis. Stem Cells. https://doi.org/10.1002/stem.2564
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