POS0374 SENESCENCE DID NOT ALTER THE CHONDROPROTECTIVE EFFECT OF EXTRACELLULAR VESICLES FROM MESENCHYMAL STROMAL CELLS
نویسندگان
چکیده
Background: Age is the most important risk factor in degenerative osteoarthritis (OA) and associated with accumulation of senescent cells that contribute to functional decline joint. We previously demonstrated extracellular vesicles (EVs) from mesenchymal stromal (MSCs) largely mediate therapeutic effect parental OA. Objectives: Here, we assessed impact senescence on characteristics EVs adipose tissue-derived MSCs (ASC-EVs) their properties an vitro model OA Methods: ASCs were induced using 25µM etoposide for 24 hours. Senescence was by quantifying proliferation rate, SA-βGal activity, nuclear γH2AX foci number, phalloidin staining expression cyclin dependent kinase inhibitors (CDKI) (RT-qPCR). ASC-EVs isolated differential ultracentrifugation characterized size, concentration, total protein content, structure (cryo-TEM) immunophenotype. In used chondrocytes patients, which stimulated IL1β 48h before culture or 7 days. Expression chondrocytic inflammatory markers quantified RT-qPCR SASP factors ELISA supernatants. Results: Senescence-induced experienced growth arrest increase staining, p21 CDKI expression, foci, stress fibers several (IL6, IL8, MMP3) confirming main features. Senescent produced 4-fold more than healthy larger. vitro, both decreased fibrotic ( type III COLLAGEN ), catabolic hypertrophic MMP3, MMP13, AP ) increased COX2 chondrocytes. By contrast, IL6 while highly . Looking at role chondrocytes, found out able AGG II they AP, X COLLAGEN, HMOX1 Finally, number positive but did not IL1β-induced Conclusion: Our results indicated a chondroprotective ASC-EVs, independently state suggested might act through different mechanisms ASCs, warrants further investigation Disclosure Interests: Jérémy Boulestreau: None declared, Marie Maumus Employee of: Bauerfeind France, Pauline Rozier: Christian Jorgensen Shareholder Medxcell sciences, Consultant Daniele Noel sciences
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Extracellular Vesicles from Adipose-Derived Mesenchymal Stem Cells Downregulate Senescence Features in Osteoarthritic Osteoblasts
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ژورنال
عنوان ژورنال: Annals of the Rheumatic Diseases
سال: 2021
ISSN: ['1468-2060', '0003-4967']
DOI: https://doi.org/10.1136/annrheumdis-2021-eular.2401