Immunosuppressive properties of cytochalasin B-induced membrane vesicles of mesenchymal stem cells : comparing with extracellular vesicles derived from mesenchymal stem cells
Autor: | Albert A. Rizvanov, Olga A. Neustroeva, Jenny L. Persson, Jennie N. Jeyapalan, N. V. Gorshkova, Sirina V. Kurbangaleeva, Sevindzh K. Kletukhina, Oksana V. Bondar, A. M. Aimaletdinov, Marina O. Gomzikova, Svetlana F. Khaiboullina, Ekaterina E. Garanina, V. V. Vorob'ev, Nigel P. Mongan, Irina Starostina |
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Jazyk: | angličtina |
Rok vydání: | 2020 |
Předmět: |
Cytochalasin B
medicine.medical_treatment lcsh:Medicine Article CCL5 Extracellular Vesicles Mice chemistry.chemical_compound Cell-Derived Microparticles In vivo medicine Animals Cytochalasin lcsh:Science Cells Cultured Multidisciplinary biology Chemistry lcsh:R CD44 Mesenchymal stem cell Immunology in the medical area Microvesicles Cytokine Immunologi inom det medicinska området Macrophages Peritoneal biology.protein Cancer research Mesenchymal stem cells Cytokines lcsh:Q Immunosuppression Immunosuppressive Agents |
Zdroj: | Scientific Reports, Vol 10, Iss 1, Pp 1-13 (2020) Scientific Reports |
ISSN: | 2045-2322 |
Popis: | 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. |
Databáze: | OpenAIRE |
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