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

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 p...

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Bibliographic Details
Published in:	Scientific reports Vol. 10; no. 1; p. 10740
Main Authors:	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.
Format:	Journal Article
Language:	English
Published:	London Nature Publishing Group UK 01-07-2020 Nature Publishing Group
Subjects:	631/250/251/1574 631/532/2074 Animals Basic Medicine CCL3 protein CD44 antigen CD45 antigen Cell-Derived Microparticles - drug effects Cell-Derived Microparticles - immunology Cells, Cultured Cerebrospinal fluid Cytochalasin B - pharmacology Cytokines Cytokines - immunology Drug delivery Erythrocytes Extracellular vesicles Extracellular Vesicles - drug effects Extracellular Vesicles - immunology Granulocyte colony-stimulating factor Granulocyte-macrophage colony-stimulating factor Humanities and Social Sciences Immunologi inom det medicinska området Immunology in the medical area Immunosuppression Immunosuppressive Agents - pharmacology Injection Interleukin 10 Interleukin 12 Interleukin 13 Interleukin 17 Interleukin 2 Interleukin 3 Interleukin 4 Interleukin 5 Interleukin 6 Interleukin 9 Kidneys Macrophages, Peritoneal - cytology Macrophages, Peritoneal - drug effects Macrophages, Peritoneal - immunology Medical and Health Sciences Medicin och hälsovetenskap Medicinska och farmaceutiska grundvetenskaper Membrane vesicles Mesenchymal stem cells Mesenchymal Stem Cells - cytology Mesenchymal Stem Cells - drug effects Mesenchymal Stem Cells - immunology Mice Monocyte chemoattractant protein 1 multidisciplinary Peritoneum Phenotypes Science Science (multidisciplinary) Spleen Stem cells
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Summary:	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.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	2045-2322 2045-2322
DOI:	10.1038/s41598-020-67563-9