Acute and chronic kidney disease is a worldwide medical and public health problem in all developped and undevelopped Countries. It is clear that a large part of the bad outcome of end-stage renal diseas (ESRD) patients is due to deficient follow-up during the earlier chronic kidney disease (CKD) stages.The concept that extracellular vesicles and exosomes (EVs) by transferring extracellular RNAs can modulate the phenotype of target cells is an emerging paradigm in the intercellular communication. The extracellular RNAs are thus now considered as paracrine/endocrine signals. EVs contain diverse species of RNAs (mRNA, miRNAs and long non-coding RNAs) reflecting the functional state of the cell of origin. Recent studies on adult stem cell-induced tissue regeneration pointed out paracrine/endocrine mechanisms rather than permanent engraftment and trans-differentiation of stem cells. Therefore, the paracrine/endocrine hypothesis has changed the perspective of the therapeutic use of stem cells in regenerative medicine. Additionally, several studies indicate that EVs play a relevant role as mediators of stem cell induced regeneration by reprogramming injured cells.Within this project, we will explore the different necessary aspects in order to get a more profound knowledge on EVs, on their mechanisms of action in tissue injury, and on the definition of the most promising “active biological ingredients” of their content to further promote EV as new potential therapeutic strategies in the field of regenerative medicine. Also, within the EVStemInjury project, two different approaches of EV production will be explored: Biological and Synthetic, showing the different potential design strategies and to assess their efficiency. Finally, in order to explore the renoprotective effect of EVs, developed within the project, ranging from toxic, ischemic and reperfusion models, we will use a large number of experimental in vitro as in vivo models of acute kidney injury.