Extracellular vesicles and exosomes from adult stem cells in the regeneration of organ injury

Introduction: EVs play a relevant role as mediators of stem cellinduced regeneration by reprogramming injured cells. The EVStemInjury project was designed to promote EVs as new potential therapeutic strategies in the field of regenerative medicine. Methods: We will seek to define the most promising ‘‘active biological ingredients’’ in the EVs, by characterizing their macromolecular content and their mechanisms of action in kidney tissue injury. To take advantage of the opportunities offered by two different design strategies, we will produce both biological and synthetic EVs and will assess their efficiency. Finally, we have planned to explore the renoprotective effect of EVs developed within the project by using a large number of experimental in vitro as well as in vivo models of acute and chronic kidney injury. Results: Four partners have joined in a consortium and are contributing to the project with different expertise and technical resources from the private sector (i.e. Fresenius Medical Care Italia S.p.A.). Dr. Ciro TETTA is the project coordinator, and the Translational Centre for Regenerative Medicine under the scientific coordination of Prof. Giovanni Camussi is performing most of the molecular and phenotypic characterization of EVs from different stem cell sources; from London Metropolitan University, Dr. Jameel INAL and the Cellular & Molecular Immunology Research Laboratory are responsible for performing 2D-DIGE analysis of MVs and exosomes and for defining biological roles of MVs in infection and cancer therapy; Dr. Raymond M. Schiffelers and the Laboratory of Clinical Chemistry & Hematology at the University Medical Centre, Utrecht, are taking charge of the manufacture or the biologic engineering of EV mimics; the Nephrology and Urology Department directed by Dr. Josep M. CAMPISTOL at Consorci Institut D’Investigacions Biome`diques August Pi I Sunyer (IDIBAPS) in Barcelona is setting up in vivo and in vitro models of CKI in combination with immunosuppressant drugs. Summary/conclusion: The studies performed will provide the bases for the pre-clinical development for the use of EVs in defined clinical conditions not only in renal diseases but also in other organ injuries, such as the liver and the heart.