title: Differential and transferable modulatory effects of mesenchymal stromal cell-derived extracellular vesicles on T, B and NK cell functions.
abstract: Mesenchymal stromal cells (MSCs) are multipotent cells, immunomodulatory stem cells that are currently used for regenerative medicine and treatment of a number of inflammatory diseases, thanks to their ability to significantly influence tissue microenvironments through the secretion of large variety of soluble factors. Recently, several groups have reported the presence of extracellular vesicles (EVs) within MSC secretoma, showing their beneficial effect in different animal models of disease. Here, we used a standardized methodological approach to dissect the immunomodulatory effects exerted by MSC-derived EVs on unfractionated peripheral blood mononuclear cells and purified T, B and NK cells. We describe here for the first time: i. direct correlation between the degree of EV-mediated immunosuppression and EV uptake by immune effector cells, a phenomenon further amplified following MSC priming with inflammatory cytokines; ii. induction in resting MSCs of immunosuppressive properties towards T cell proliferation through EVs obtained from primed MSCs, without any direct inhibitory effect towards T cell division. Our conclusion is that the use of reproducible and validated assays is not only useful to characterize the mechanisms of action of MSC-derived EVs, but is also capable of justifying EV potential use as alternative cell-free therapy for the treatment of human inflammatory diseases.
authors.affiliation: Stem Cell Research Laboratory, Section of Hematology, Department of Medicine, University of Verona, Italy.
authors.forename: Mariano
authors.initials: M
authors.lastname: Di Trapani
authors.affiliation: Stem Cell Research Laboratory, Section of Hematology, Department of Medicine, University of Verona, Italy.
authors.forename: Giulio
authors.initials: G
authors.lastname: Bassi
authors.affiliation: Stem Cell Research Laboratory, Section of Hematology, Department of Medicine, University of Verona, Italy.
authors.forename: Martina
authors.initials: M
authors.lastname: Midolo
authors.affiliation: Stem Cell Research Laboratory, Section of Hematology, Department of Medicine, University of Verona, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Gatti
authors.affiliation: Stem Cell Research Laboratory, Section of Hematology, Department of Medicine, University of Verona, Italy.
authors.forename: Paul Takam
authors.initials: PT
authors.lastname: Kamga
authors.affiliation: Stem Cell Research Laboratory, Section of Hematology, Department of Medicine, University of Verona, Italy.
authors.forename: Adriana
authors.initials: A
authors.lastname: Cassaro
authors.affiliation: Stem Cell Research Laboratory, Section of Hematology, Department of Medicine, University of Verona, Italy.
authors.forename: Roberta
authors.initials: R
authors.lastname: Carusone
authors.affiliation: Stem Cell Research Laboratory, Section of Hematology, Department of Medicine, University of Verona, Italy.
authors.forename: Annalisa
authors.initials: A
authors.lastname: Adamo
authors.affiliation: Stem Cell Research Laboratory, Section of Hematology, Department of Medicine, University of Verona, Italy.
authors.forename: Mauro
authors.initials: M
authors.lastname: Krampera
mesh_terms: D001402:B-Lymphocytes / Q000276:immunology*; D002478:Cells, Cultured; D045142:Cross-Priming; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D000067128:Extracellular Vesicles / Q000276:immunology*; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology*; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D016207:Cytokines