Extracellular Vesicles Mediate Mesenchymal Stromal Cell-Dependent Regulation of B Cell PI3K-AKT Signaling Pathway and Actin Cytoskeleton

Annalisa Adamo, Jessica Brandi, Simone Caligola, Pietro Delfino, Riccardo Bazzoni, Roberta Carusone, Daniela Cecconi, Rosalba Giugno, Marcello Manfredi, Elisa Robotti, Emilio Marengo, Giulio Bassi, Paul Takam Kamga, Giada Dal Collo, Alessandro Gatti, Angela Mercuri, Maddalena Arigoni, Martina Olivero, Raffaele A Calogero, Mauro Krampera*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

67 Citations (Scopus)
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Mesenchymal stromal cells (MSCs) are adult, multipotent cells of mesodermal origin representing the progenitors of all stromal tissues. MSCs possess significant and broad immunomodulatory functions affecting both adaptive and innate immune responses once MSCs are primed by the inflammatory microenvironment. Recently, the role of extracellular vesicles (EVs) in mediating the therapeutic effects of MSCs has been recognized. Nevertheless, the molecular mechanisms responsible for the immunomodulatory properties of MSC-derived EVs (MSC-EVs) are still poorly characterized. Therefore, we carried out a molecular characterization of MSC-EV content by high-throughput approaches. We analyzed miRNA and protein expression profile in cellular and vesicular compartments both in normal and inflammatory conditions. We found several proteins and miRNAs involved in immunological processes, such as MOES, LG3BP, PTX3, and S10A6 proteins, miR-155-5p, and miR-497-5p. Different in silico approaches were also performed to correlate miRNA and protein expression profile and then to evaluate the putative molecules or pathways involved in immunoregulatory properties mediated by MSC-EVs. PI3K-AKT signaling pathway and the regulation of actin cytoskeleton were identified and functionally validated in vitro as key mediators of MSC/B cell communication mediated by MSC-EVs. In conclusion, we identified different molecules and pathways responsible for immunoregulatory properties mediated by MSC-EVs, thus identifying novel therapeutic targets as safer and more useful alternatives to cell or EV-based therapeutic approaches.

Original languageEnglish
Pages (from-to)446
JournalFrontiers in Immunology
Publication statusPublished - 2019
Externally publishedYes


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