Paracrine roles of extracellular vesicles released by mouse mesoangioblasts

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Abstract

Extracellular vesicles (EV) represent an important mediator ofcell-to-cell communication and are involved in both autocrineand paracrine signaling, with a critical role in a number of physiologicaland pathological conditions.1 The bioactive moleculescontained within EV simultaneously activate several differentpathways resulting in the synergistic stimulation of target cells.The discovery and characterization of EV have added a novelunderstanding to regenerative medicine, namely the finding thatstem cells are an abundant source of EV.1-2 A6 mouse mesoangioblasts,vessel-associated multipotent progenitor stem cellsthat are capable of differentiating into different mesodermalcell types, are able to release in the extracellular environmentmembrane vesicles, which contain structural proteins, FGF-2 and the two gelatinases MMP2 and MMP9.3 Moreover, we havealready demonstrated that EV released by these cells containHsp70 as a transmembrane protein, which is involved in anautocrine signaling responsible for increased cell migration.4 Inthis study we have investigated the possible paracrine effects ofA6 derived EV with other cell types, and the effects of theseinteractions. Firstly, we have focused our attention on theirinteraplay capacity with human endothelial cells, which areinduced to form capillary-like structures in vitro and to increasetheir motility. Furthermore, we have analyzed EV immunomodulatoryeffect on Jurkat lymphocytes, demonstrating that theyare able to inhibit both their activation and proliferation.Finally, we have investigated the role of sugar residues on themembrane of A6 derived EV in their interaction with other celltypes, by enzymatic removing of N-linked glycans on their membrane.In particular, PNGase F that is responsible for the cleavagebetween asparagine and GlcNAc in all types of glycanchains induces a substantial reduction in EV-target cell interaction.On the contrary, the use of EndoH, which is responsible forthe cleavage between two residues of GlcNAc, increase targetcell-EV interaction.
Lingua originaleEnglish
pagine (da-a)4-4
Numero di pagine1
RivistaEUROPEAN JOURNAL OF HISTOCHEMISTRY
Volume61/supplement 1
Stato di pubblicazionePublished - 2017

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