| Popis: |
Extracellular vesicles (EV) represent an important mediator of cell-to-cell communication and are involved in both autocrine and paracrine signaling, with a critical role in a number of physiological and pathological conditions.1 The bioactive molecules contained within EV simultaneously activate several different pathways resulting in the synergistic stimulation of target cells. The discovery and characterization of EV have added a novel understanding to regenerative medicine, namely the finding that stem cells are an abundant source of EV.1-2 A6 mouse mesoangioblasts, vessel-associated multipotent progenitor stem cells that are capable of differentiating into different mesodermal cell types, are able to release in the extracellular environment membrane vesicles, which contain structural proteins, FGF-2 and the two gelatinases MMP2 and MMP9.3 Moreover, we have already demonstrated that EV released by these cells contain Hsp70 as a transmembrane protein, which is involved in an autocrine signaling responsible for increased cell migration.4 In this study we have investigated the possible paracrine effects of A6 derived EV with other cell types, and the effects of these interactions. Firstly, we have focused our attention on their interaplay capacity with human endothelial cells, which are induced to form capillary-like structures in vitro and to increase their motility. Furthermore, we have analyzed EV immunomodulatory effect on Jurkat lymphocytes, demonstrating that they are able to inhibit both their activation and proliferation. Finally, we have investigated the role of sugar residues on the membrane of A6 derived EV in their interaction with other cell types, by enzymatic removing of N-linked glycans on their membrane. In particular, PNGase F that is responsible for the cleavage between asparagine and GlcNAc in all types of glycan chains induces a substantial reduction in EV-target cell interaction. On the contrary, the use of EndoH, which is responsible for the cleavage between two residues of GlcNAc, increase target cell-EV interaction. |
