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Immunosuppressive properties of cytochalasin B-induced membrane vesicles of mesenchymal stem cells: comparing with extracellular vesicles derived from mesenchymal stem cells

Gomzikova, M. O.; Aimaletdinov, A. M.; Bondar, O. V.; Starostina, I. G.; Gorshkova, N. V.; Neustroeva, O. A.; Kletukhina, S. K.; Kurbangaleeva, S. V.; Vorobev, V. V.; Garanina, E. E.; Persson, J. L.; Jeyapalan, J.; Mongan, N. P.; Khaiboullina, S. F.; Rizvanov, A. A.

Authors

M. O. Gomzikova

A. M. Aimaletdinov

O. V. Bondar

I. G. Starostina

N. V. Gorshkova

O. A. Neustroeva

S. K. Kletukhina

S. V. Kurbangaleeva

V. V. Vorobev

E. E. Garanina

J. L. Persson

S. F. Khaiboullina

A. A. Rizvanov



Abstract

Extracellular vesicles derived from mesenchymal stem cells (MSCs) represent a novel approach for regenerative and immunosuppressive therapy. Recently, cytochalasin B-induced microvesicles (CIMVs) were shown to be effective drug delivery mediators. However, little is known about their immunological properties. We propose that the immunophenotype and molecular composition of these vesicles could contribute to the therapeutic efficacy of CIMVs. To address this issue, CIMVs were generated from murine MSC (CIMVs-MSCs) and their cytokine content and surface marker expression determined. For the first time, we show that CIMVs-MSCs retain parental MSCs phenotype (Sca-1+, CD49e+, CD44+, CD45-). Also, CIMVs-MSCs contained a cytokine repertoire reflective of the parental MSCs, including IL-1β, IL-2, IL-3, IL-4, IL-5, IL-6, IL-9, IL-10, IL-12(p40), IL-13, IL-17, CCL2, CCL3, CCL4, CCL5, CCL11, G-CSF, GM-CSF and TNF-α. Next, we evaluated the immune-modulating properties of CIMVs-MSCs in vivo using standard preclinical tests. MSCs and CIMVs-MSCs reduced serum levels of anti-sheep red blood cell antibody and have limited effects on neutrophil and peritoneal macrophage activity. We compared the immunomodulatory effect of MSCs, CIMVs and EVs. We observed no immunosuppression in mice pretreated with natural EVs, whereas MSCs and CIMVs-MSCs suppressed antibody production in vivo. Additionally, we have investigated the biodistribution of CIMVs-MSCs in vivo and demonstrated that CIMVs-MSCs localized in liver, lung, brain, heart, spleen and kidneys 48 h after intravenous injection and can be detected 14 days after subcutaneous and intramuscular injection. Collectively our data demonstrates immunomodulatory efficacy of CIMVs and supports their further preclinical testing as an effective therapeutic delivery modality.

Journal Article Type Article
Publication Date Jul 1, 2020
Journal Scientific Reports
Print ISSN 2045-2322
Electronic ISSN 2045-2322
Publisher Nature Publishing Group
Peer Reviewed Peer Reviewed
Volume 10
Article Number 10740
APA6 Citation Gomzikova, M. O., Aimaletdinov, A. M., Bondar, O. V., Starostina, I. G., Gorshkova, N. V., Neustroeva, O. A., …Rizvanov, A. A. (2020). Immunosuppressive properties of cytochalasin B-induced membrane vesicles of mesenchymal stem cells: comparing with extracellular vesicles derived from mesenchymal stem cells. Scientific Reports, 10, https://doi.org/10.1038/s41598-020-67563-9
DOI https://doi.org/10.1038/s41598-020-67563-9
Publisher URL https://www.nature.com/articles/s41598-020-67563-9
Additional Information Received: 26 April 2019; Accepted: 5 June 2020; First Online: 1 July 2020; : The authors declare no competing interests.

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