Extracellular vesicles shedded by mouse mesoangioblasts have paracrine effects on different cell types

Abstract

Introduction Mouse mesoangioblasts are vessel associated progenitor stem cells endowed with the ability of multipotent mesoderm differentiation. We have already demonstrated that these stem cells, as all the other stem cells, are able to release in the extracellular milieu membrane vesicles (EV) containing biological active molecules, such as FGF2, MMP2/91 and Hsp702. Today takes hold the idea that the vesicles can replace stem cells opening a new scenario in regenerative medicine3. To this aim, we investigated the possible paracrine interaction of mesoangioblast EV on different cell types and their effects. Results and conclusions We have showed that mesoangioblast EV interact with human endothelial cells by in vitro inducing their differentiation versus capillary-like structures, and increasing their migration capability. In addition, we have analyzed the immunomodulatory effect of EV on human lymphocytes. We have demonstrated that EV are able to inhibit both lymphocyte activation and proliferation. Finally, we started to investigate the mechanisms of interaction between EV and target cells. In particular, we have observed the involvement of EV saccharidic residues in cell targeting. The enzymatic removal of EV N-lynked glycans by PNGase F, which cleaves between asparagine and GlcNAc in all types of glycan chains, induces a substantial reduction in EV-target cell interaction. Conversely, EndoH that is responsible for the cleavage between two residues of GlcNAc increases this interaction. In conclusion, saccharidic residues exert a role in EV-cell interplay. References 1 Candela ME et al. J Cell Physiol 2010, 224: 144-51. 2 Barreca MM et al. J Cell Physiol. 2017, 232: 1845-61. 3 Tetta C et al. Endocrine 2013, 44: 11-19.