Extracellular Vesicles from Cardiac Progenitor Cells (CPCs) and their role in cardiac regeneration

Regenerative medicine is a research field based on the use of stem cells, gene therapy and tissue engineering aiming to replace, repair or regenerate injured tissues and organs with healthy ones. At first, regenerative medicine focused on stem cells, in virtue of their self-renewal and of their ability to differentiate in other cell types. Recently, as paracrine mechanism appears to be responsible for the observed activity of stem cells, researchers focused on extracellular vesicles (EVs). EVs are nanosized structures composed by a bilayer membrane which contains several molecules such as proteins, nucleic acids, lipids and metabolites. Among cardiovascular diseases, myocardial infarction represents one of the major causes of death worldwide. In the present thesis work, I will highlight examples of the current literature on the therapeutic use of stem cell-EVs in cardiac regeneration. It was demonstrated that EVs originating from mesenchymal cardiac progenitors stimulated angiogenesis and migration of endothelial cells through the activation of the MAPK and Ang-1-Tie-2 pathways. Moreover, cardiovascular progenitor-derived EVs were reported to display anti-inflammatory effects in heart damage. Finally, the ability of induced Pluripotent Stem-derived Cardiac Progenitor cell- EVs to limit fibrosis in murine models of infarction and the role of microRNA cargo was reported. Currently EVs, in the regenerative medicine field, represent a promising treatment for several diseases, both monogenic and multifactorial. Further studies are needed to completely understand the features of the EVs and their mechanism of action, but future advances in this field may change all the established treatments.