H fused to an EV-sorting moiety. The engineered decoy EVs, subsequently isolated from conditioned media,

H fused to an EV-sorting moiety. The engineered decoy EVs, subsequently isolated from conditioned media, have been evaluated using reporter cell lines, stimulated by either IL-6-IL-6R complexes or TNF-alpha with a luminescentISEV 2018 abstract bookor fluorescent reporter read-out for the respective cytokine. The therapeutic possible of decoy EVs have been further evaluated in vivo, in 3 diverse inflammatory mouse models. Results: In vitro, the outcomes demonstrated dose-dependent inhibition of decoy EVs on respective cytokine pathways. Subsequent, the effects of decoy EVs in vivo were evaluated within a TNBS-colitis model and a LPS-induced systemic inflammation mouse model, displaying protective effects with enhanced survival and decreased weight reduction. To additional assess the potential of decoy EVs on inhibiting pro-inflammatory pathways, decoy EVs were evaluated inside a numerous sclerosis model, experimental autoimmune encephalomyelitis (EAE). Mice induced with EAE and treated with decoy EVs displayed substantially milder symptoms when compared to mock manage therapy. Summary/Conclusion: In conclusion, by combining the helpful effects of stem cell therapies and protein therapeutics, engineered decoy EVs might have terrific potential to become the following generation of biotherapeutics.LBT01.Improvement of a standardized exosome production process for clinical use S by means of C. Rodrigues; Renato Cardoso; Filipe Death-Associated Protein Kinase 3 (DAPK3) Proteins Recombinant Proteins Duarte; Cl dia O. Gomes; Joana Sim s Correia Exogenus Therapeutics, SA, Cantanhede, PortugalBackground: Exogenus Gag-Pol Polyprotein Proteins Accession Therapeutics is building new therapeutic tools for the therapy of skin diseases, depending on exosomes secreted by umbilical cord blood (UCB) cells. Guaranteeing manufacturing of clinicalgrade vesicles beneath GMP, even though improve homogeneity and scalability in the item batches, is actually a main challenge inside the field of EV-inspired therapeutics. Methods: We have implemented various changes to the manufacturing workflow of our lead product Exo-101 namely integration of Automatic UCB Processing (AP), implementation of an exosome purification technique according to Ultrafiltration and Chromatography (UF-SEC), combined with pooling from various donors. We evaluated the effect of these alterations by validating the biophysical and biomolecular qualities of Exo-101 (by NTA, TEM, flow cytometry and qPCR). The therapeutic possible was confirmed on a delayed wound healing mice model. Outcomes: We demonstrate that independently of utilizing manual (MP) or automatic (AP) UCB processing, the purified exosomes are extremely comparable in size (MP 150.2.0 nm and AP 152.four.five nm), particularly enriched in particles with 5000 nm (75), and express classical and nonclassical markers including CD9, CD63 and CD15. The UF-SEC primarily based manufacturing process, combined with donors’ pooling, leads to greater Exo-101 yield. Importantly, this GMP-compliant version of Exo-101 has enhanced regenerative possible, enhancing the acceleration of wound closure as from day three, top to 20 improvement at day ten. Summary/Conclusion: We have been prosperous in optimizing a standardized GMP-compliant procedure for the production of clinical-grade exosomes. With this experience, Exogenus Therapeutics is in a privileged position to help other organizations and investigation groups in transforming R D-based purification processes into controlled manufacturing of exosomes for clinical use. Funding: This function was co-funded by Centro 2020 – Regional Operational System, Portugal 2020 and European Union by way of FEDER.complexes (.