title: Immunoregulatory Effects of Mesenchymal Stem Cell-Derived Extracellular Vesicles on T Lymphocytes.
abstract: The immunomodulatory activity of mesenchymal stem cells (MSCs) is largely mediated by paracrine factors. We have recently shown that the immunosuppressive effects of MSCs on B lymphocytes in peripheral blood mononuclear cell (PBMC) culture can be reproduced by extracellular vesicles (EVs) isolated from MSC culture supernatants. Here we investigated the effect of bone marrow-derived MSC-EVs on T cells on PBMC cultures stimulated with anti-CD3/CD28 beads. Stimulation increased the number of proliferating CD3(+) cells as well as of regulatory T cells (Tregs). Coculture with MSCs inhibited the proliferation of CD3(+) cells, with no significant changes in apoptosis. Addition of MSC-EVs to PBMCs did not affect proliferation of CD3(+) cells, but induced the apoptosis of CD3(+) cells and of the CD4(+) subpopulation and increased the proliferation and the apoptosis of Tregs. Moreover, MSC-EV treatment increased the Treg/Teff ratio and the immunosuppressive cytokine IL-10 concentration in culture medium. The activity of indoleamine 2,3-dioxygenase (IDO), an established mediator of MSC immunosuppressive effects, was increased in supernatants of PBMCs cocultured with MSCs, but was not affected by the presence of MSC-EVs. MSC-EVs demonstrate immunomodulatory effects on T cells in vitro. However, these effects and the underlying mechanisms appear to be different from those exhibited by their cells of origin.
authors.affiliation: Regenerative Medicine, Bambino Gesù Children's Hospital, Rome, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Del Fattore
authors.forename: Rosa
authors.initials: R
authors.lastname: Luciano
authors.forename: Luisa
authors.initials: L
authors.lastname: Pascucci
authors.forename: Bianca Maria
authors.initials: BM
authors.lastname: Goffredo
authors.forename: Ezio
authors.initials: E
authors.lastname: Giorda
authors.forename: Margherita
authors.initials: M
authors.lastname: Scapaticci
authors.forename: Alessandra
authors.initials: A
authors.lastname: Fierabracci
authors.forename: Maurizio
authors.initials: M
authors.lastname: Muraca
mesh_terms: D000328:Adult; D017209:Apoptosis / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology*; D001854:Bone Marrow Cells / Q000166:cytology / Q000276:immunology; D017252:CD3 Complex / Q000276:immunology; D002352:Carrier Proteins / Q000276:immunology; D049109:Cell Proliferation / Q000502:physiology; D002478:Cells, Cultured; D018920:Coculture Techniques; D000067128:Extracellular Vesicles / Q000276:immunology*; D005260:Female; D006801:Humans; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000378:metabolism; D016753:Interleukin-10 / Q000378:metabolism; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000276:immunology*; D011994:Recombinant Proteins / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D055815:Young Adult
chemical_list: C468140:CD28-binding protein, human; D017252:CD3 Complex; D002352:Carrier Proteins; C508609:IL10 protein, human; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D011994:Recombinant Proteins; D016753:Interleukin-10