Immunosuppressive properties of cytochalasin B-induced membrane vesicles of mesenchymal stem cells : comparing with extracellular vesicles derived from mesenchymal stem cells
(2020) In Scientific Reports 10(1).- 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,... (More)
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.
(Less)
- author
- organization
- publishing date
- 2020
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Scientific Reports
- volume
- 10
- issue
- 1
- article number
- 10740
- publisher
- Nature Publishing Group
- external identifiers
-
- pmid:32612100
- scopus:85087217503
- ISSN
- 2045-2322
- DOI
- 10.1038/s41598-020-67563-9
- language
- English
- LU publication?
- yes
- id
- b421c6b3-a744-4dc8-9562-d6ad185a0a2f
- date added to LUP
- 2020-07-14 11:07:35
- date last changed
- 2024-06-26 18:53:01
@article{b421c6b3-a744-4dc8-9562-d6ad185a0a2f,
abstract = {{<p>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<sup>+</sup>, CD49e<sup>+</sup>, CD44<sup>+</sup>, CD45<sup>−</sup>). 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.</p>}},
author = {{Gomzikova, M. O. and Aimaletdinov, A. M. and Bondar, O. V. and Starostina, I. G. and Gorshkova, N. V. and Neustroeva, O. A. and Kletukhina, S. K. and Kurbangaleeva, S. V. and Vorobev, V. V. and Garanina, E. E. and Persson, J. L. and Jeyapalan, J. and Mongan, N. P. and Khaiboullina, S. F. and Rizvanov, A. A.}},
issn = {{2045-2322}},
language = {{eng}},
number = {{1}},
publisher = {{Nature Publishing Group}},
series = {{Scientific Reports}},
title = {{Immunosuppressive properties of cytochalasin B-induced membrane vesicles of mesenchymal stem cells : comparing with extracellular vesicles derived from mesenchymal stem cells}},
url = {{http://dx.doi.org/10.1038/s41598-020-67563-9}},
doi = {{10.1038/s41598-020-67563-9}},
volume = {{10}},
year = {{2020}},
}