title: The immunosuppressive effect of mesenchymal stromal cells on B lymphocytes is mediated by membrane vesicles.
abstract: The immunomodulatory properties of mesenchymal stromal cells are the subject of increasing interest and of widening clinical applications, but the reproducibility of their effects is controversial and the underlying mechanisms have not been fully clarified. We investigated the transfer  of membrane vesicles, a recently recognized pathway of intercellular communication, as possible mediator of the interaction between mesenchymal stromal cells and B lymphocytes. Mesenchymal stromal cells exhibited a strong dose-dependent inhibition of B-cell proliferation and differentiation  in a CpG-stimulated peripheral blood mononuclear cell coculture system. We observed that these effects could be fully reproduced by membrane vesicles isolated from mesenchymal stromal cell culture supernatants in a dose-dependent fashion. Next, we evaluated the localization of fluorescently  labeled membrane vesicles within specific cell subtypes both by flow cytometry and by confocal microscopy analysis. Membrane vesicles were found to be associated with stimulated B lymphocytes, but not with other cell phenotypes (T lymphocytes, dendritic cells, natural killer cells), in peripheral  blood mononuclear cell culture. These results suggest that membrane vesicles derived from mesenchymal stromal cells are the conveyors of the immunosuppressive effect on B lymphocytes. These particles should be further evaluated as immunosuppressive agents in place of the parent cells, with  possible advantages in term of standardization, safety, and feasibility.
authors: Research Laboratories, Children's Hospital Bambino Gesù Research Institute, 00165 Rome, Italy.
authors: Manuela
authors: M
authors: Budoni
authors: Alessandra
authors: A
authors: Fierabracci
authors: Rosa
authors: R
authors: Luciano
authors: Stefania
authors: S
authors: Petrini
authors: Vincenzo
authors: V
authors: Di Ciommo
authors: Maurizio
authors: M
authors: Muraca
mesh_terms: D017209:Apoptosis / Q000276:immunology; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology*; D002450:Cell Communication / Q000276:immunology*; D002454:Cell Differentiation / Q000276:immunology; D048708:Cell Growth Processes / Q000276:immunology; D055252:Cell-Derived Microparticles / Q000276:immunology; D018920:Coculture Techniques; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000276:immunology*