H fused to an EV-sorting moiety. The engineered decoy EVs, subsequently isolated from conditioned media, had been evaluated employing 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 had been additional evaluated in vivo, in 3 distinctive inflammatory mouse models. Benefits: In vitro, the results demonstrated dose-dependent inhibition of decoy EVs on respective cytokine pathways. Subsequent, the effects of decoy EVs in vivo had been evaluated in a TNBS-colitis model and also a LPS-Cathepsin H Proteins Accession induced systemic inflammation mouse model, displaying protective effects with increased survival and decreased weight-loss. To additional assess the potential of decoy EVs on inhibiting pro-inflammatory pathways, decoy EVs were evaluated within a various sclerosis model, experimental autoimmune encephalomyelitis (EAE). Mice induced with EAE and treated with decoy EVs displayed considerably milder symptoms when in comparison to mock handle treatment. Summary/Conclusion: In conclusion, by combining the Hemagglutinin-Neuraminidase Proteins Biological Activity helpful effects of stem cell therapies and protein therapeutics, engineered decoy EVs might have fantastic prospective to be the subsequent generation of biotherapeutics.LBT01.Development of a standardized exosome production approach for clinical use S by means of C. Rodrigues; Renato Cardoso; Filipe Duarte; Cl dia O. Gomes; Joana Sim s Correia Exogenus Therapeutics, SA, Cantanhede, PortugalBackground: Exogenus Therapeutics is establishing new therapeutic tools for the treatment of skin ailments, according to exosomes secreted by umbilical cord blood (UCB) cells. Making sure manufacturing of clinicalgrade vesicles under GMP, whilst increase homogeneity and scalability in the solution batches, is a significant challenge in the field of EV-inspired therapeutics. Strategies: We’ve got implemented various modifications towards the manufacturing workflow of our lead solution Exo-101 namely integration of Automatic UCB Processing (AP), implementation of an exosome purification strategy according to Ultrafiltration and Chromatography (UF-SEC), combined with pooling from diverse donors. We evaluated the influence of these alterations by validating the biophysical and biomolecular qualities of Exo-101 (by NTA, TEM, flow cytometry and qPCR). The therapeutic prospective was confirmed on a delayed wound healing mice model. Benefits: We demonstrate that independently of applying manual (MP) or automatic (AP) UCB processing, the purified exosomes are extremely related in size (MP 150.two.0 nm and AP 152.4.five nm), specifically enriched in particles with 5000 nm (75), and express classical and nonclassical markers such as CD9, CD63 and CD15. The UF-SEC primarily based manufacturing process, combined with donors’ pooling, results in higher Exo-101 yield. Importantly, this GMP-compliant version of Exo-101 has enhanced regenerative possible, enhancing the acceleration of wound closure as from day 3, leading to 20 improvement at day ten. Summary/Conclusion: We have been successful in optimizing a standardized GMP-compliant course of action for the production of clinical-grade exosomes. With this expertise, Exogenus Therapeutics is in a privileged position to help other providers and analysis groups in transforming R D-based purification processes into controlled manufacturing of exosomes for clinical use. Funding: This perform was co-funded by Centro 2020 – Regional Operational Program, Portugal 2020 and European Union via FEDER.complexes (.
