MiR199a and miR126 in myocardium following ischemia, which has to be tested in further experiments in vivo. Funding: This study is funded by National Science Centre Poland (NCN) Caspase 1 Chemical Storage & Stability grants: SONATA BIS-3 (UMO-2013/10/E/NZ3/007500) to EZS and PRELUDIUM-11 (UMO-2016/21/N/NZ3/00363) to KKW. Faculty of Biochemistry, Biophysics and Biotechnology of Jagiellonian University is often a partner on the Major National Analysis Center (KNOW) supported by the Ministry of Science and Larger EducationThursday, 03 MayPT07: EV-inspired Therapeutics, Vaccines, and Clinical Trials Chairs: Shilpa Buch; Pia Siljander Location: Exhibit Hall 17:158:PT07.Extrusion of mesenchymal stromal cells produces EV-like vesicles that attenuate allergic airway inflammation Elga Bandeira1; Su Chul Jang2; Kyong-Su Park1; Kristina Johansson1; Cecilia L ser3; Madeleine R inger1; Jan L vall1 University of Gothenburg, Gothenburg, Sweden; 2Krefting Study Centre, Institute of Medicine, University of Gothenburg, Boston, USA; 3Krefting Analysis Centre, Institute of Medicine, University of Gothenburg, Gothenburg, SwedenBackground: Asthma is connected with airflow obstruction and hyperresponsiveness that arises from airway inflammation and remodelling. Cell therapy with mesenchymal stromal cells (MSC) has been shown to attenuate airway inflammation in asthma models. Not too long ago, comparable effects have been observed working with extracellular vesicles (EVs) released by these cells. Nano-sized vesicles also can be artificially generated from MSC by extrusion, and we contact them exosome-mimetic nanovesicles (NVs). Within this study, we evaluated the effects of MSC-derived EVs and NVs within a murine model of allergic airway inflammation. Methods: EVs have been obtained via sequential centrifugation of media conditioned by human bone marrow MSC for 24 h. NVs had been created via serial extrusion of MSCs. Both vesicle types underwent density gradient purification and were quantified via nanoparticle tracking evaluation. C57Bl/6 mice were sensitized to ovalbumin (OVA), randomly divided into OVA (intranasally exposed to 100 OVA on five CaMK II Inhibitor Purity & Documentation consecutive days) and manage (exposed to PBS) groups. The mice had been further randomized into groups that received 2E09 EVs or NVs, following the initial OVA/PBS exposure. Outcomes: Regional administration of each EVs and NVs decreased the cellularity and number of eosinophils in bronchoalveolar lavage fluid (BALF) of OVA-exposed animals. Moreover, NVs brought on a decrease within the quantity of inflammatory cells within the lung tissue, which was related with lower levels of CCL24 in BALF and lung tissue. The effectivity of NVs was similar when administered intraperitoneally or locally for the airways. Altering the administration route, nevertheless, led to exceptional differences in their biodistribution and to distinct attenuation specially of IL-13 and CCL24. Summary/conclusion: Our results indicate that EVs and NVs derived from MSC have comparable effects within a murine model of airway allergy. Moreover, artificially generated vesicles could be efficient upon diverse delivery routes, which, even so, results in unique immunomodulatory effects. As a result of the higher yield of vesicles obtained by the extrusion course of action and the technical benefits it presents, we recommend that NVs is usually an option to EVs in MSC-based therapies. Funding: The Swedish Heart-Lung Foundation, Sahlgrenska University Hospital, Herman Krefting Foundation Against Asthma/Allergy, CODIAK Biosciences.Exosomes are native se.
