Functional Characterization of Mesenchymal Stromal Cell- Derived Extracellular Vesicles

Mesenchymal Stromal Cells (MSCs) are currently considered a powerful tool for the treatment of multiple diseases. Indeed, the original hypothesis underlying MSC based regenerative therapies was based on functional recovery as a consequence of stem cell differentiation. But it is now clear that other mechanisms of action are involved. The recent emerging paradigm shift suggests that the paracrine effects of MSCs may be as important as cell differentiation in eliciting functional tissue repair. Among the factors responsible for the paracrine effects, extracellular vesicles (EVs) have been recently described as new players in cell-cell communication, as mediators of proteins, lipids, and genetic information. MSCs derived-EVs showed to be involved in a wide spread of processes, including angiogenesis, senescence, proliferation, and differentiation, beside strong immunomodulatory properties, and a key role in tissue homeostasis. The aim of this thesis is to characterize EVs released by MSCs to investigate their involvement as modulators of MSC paracrine effects. Exploiting this natural intercellular signaling mechanism could be beneficial to overcome some important limitations of cell therapies and, in this scenario, they could represent an efficient therapeutic vehicle for regenerative medicine.