Otentially damaging plasmid DNA and off-target toxicity. The findings move this strategy closer to clinical transfer. Funding: NIH NCATS UH3TR000902.OF11.High yield hMSC derived mechanically induced xenografted extracellular vesicles are properly tolerated and induce potent regenerative effect in vivo in local or IV injection in a model of chronic heart failure Max Piffouxa, Iris Marangonb, Nathalie Mougenotc, Claire Wilhelmd, Florence Gazeaue, Onnik Agbulutf and Amanda Brun-Silvaga Laboratoire Mati e et Syst es LIGHT Proteins Recombinant Proteins Complexes, CNRS UMR 7047 UniversitParis Diderot, Paris, France; bUniversitSorbonne Paris Cit Laboratoire Mati e et Syst es Complexes, CNRS UMR 7047 UniversitParis Diderot, France; cSorbonne Universit , UniversitPierre et Marie Curie Paris 6, Plateforme PECMV, UMS28, Paris, France; dlaboratoire Mati e et Syst es Complexes, paris, France; eUniversitSorbonne Paris Cit Laboratoire Mati e et Syst es Complexes, CNRS UMR 7047 UniversitParis Diderot, Paris, France; fUniversitSorbonne Paris Cit Laboratoire Mati e et Syst es Complexes, CNRS UMR 7047 UniversitParis Diderot, Paris, France; 7UniversitSorbonne Paris Cit Laboratoire Mati e et Syst es Complexes, CNRS UMR 7047 UniversitParis Diderot, Paris, FranceIntroduction: Around the road towards the usage of extracellular vesicles (EVs) for regenerative medicine, technological hurdles remain unsolved: high-yield, high purity and cost-effective production of EVs. Techniques: Pursuing the analogy with shear-stress induced EV release in blood, we’re creating a mechanical-stress EV triggering cell culture strategy in scalable and GMP-compliant bioreactors for costeffective and high yield EV production. The third generation setup makes it possible for the production of up to 300,000 EVs per Mesenchymal Stem Cell, a 100-fold improve in comparison with classical strategies, i.e physiological spontaneous release in depleted media (about 2000 EVs/ cell), using a higher purity ratio 1 10e10 p/ Benefits: We investigated in vitro the regenerative IgG2 Proteins manufacturer prospective of higher yield mechanically induced MSC-EVs by demonstrating an equal or improved efficiency in comparison with classical EVs with the very same quantity of EVs. The regenerative properties of mechanically induced MSCEVs was confirmed in vivo within a murine model of chronic heart failure demonstrating that higher, medium shear strain EVs and serum starvation EVs or mMSCs had precisely the same effect working with nearby injection. We later on tested the effect of your injection route along with the use of xenogenic hMSC-EVs on their efficiency in the similar model of murine chronic heart failure. Heart functional parameters have been analysed by ultrasound 2 months (1 month post EV injection) post infarction. Interestingly, hMSCEVs had exactly the same impact when compared with mMSC-EVs in neighborhood injection, showing that xeno-EVs in immunocompetent mices was properly tolerated. Furthermore, hMSC EV IV injection was as effective as regional intra-myocardium muscle injection with a rise inside the left ventricular ejection fraction of 26 in comparison with pre-treatment values, whereas PBS injected controls lost 13 . Summary/Conclusion: We demonstrated an equal or superior regenerative impact of high yield mechanically developed EVs when compared with spontaneously released EVs or parental cells in vitro and in vivo, and fantastic tolerance and efficacy of hMSC EV both with local and IV injection. This exclusive technologies for EV production combines decisive assets for clinical translation of EV-based regenerative medicine : a GMP-compliant setup, high density cell culture, higher yield re.