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Effects of Extracellular Vesicles from Blood-Derived Products on Osteoarthritic Chondrocytes within an Inflammation Model
Authors:Alexander Otahal  Karina Kramer  Olga Kuten-Pella  Lukas B Moser  Markus Neubauer  Zsombor Lacza  Stefan Nehrer  Andrea De Luna
Affiliation:1.Center for Regenerative Medicine, Danube University Krems, 3500 Krems, Austria; (K.K.); (L.B.M.); (M.N.); (S.N.); (A.D.L.);2.OrthoSera GmbH, 3500 Krems, Austria; (O.K.-P.); (Z.L.);3.Institute of Sport and Health Sciences, University of Physical Education, 1123 Budapest, Hungary
Abstract:Osteoarthritis (OA) is hallmarked by a progressive degradation of articular cartilage. One major driver of OA is inflammation, in which cytokines such as IL-6, TNF-α and IL-1β are secreted by activated chondrocytes, as well as synovial cells—including macrophages. Intra-articular injection of blood products—such as citrate-anticoagulated plasma (CPRP), hyperacute serum (hypACT), and extracellular vesicles (EVs) isolated from blood products—is gaining increasing importance in regenerative medicine for the treatment of OA. A co-culture system of primary OA chondrocytes and activated M1 macrophages was developed to model an OA joint in order to observe the effects of EVs in modulating the inflammatory environment. Primary OA chondrocytes were obtained from patients undergoing total knee replacement. Primary monocytes obtained from voluntary healthy donors and the monocytic cell line THP-1 were differentiated and activated into proinflammatory M1 macrophages. EVs were isolated by ultracentrifugation and characterized by nanoparticle tracking analysis and Western blot. Gene expression analysis of chondrocytes by RT-qPCR revealed increased type II collagen expression, while cytokine profiling via ELISA showed lower TNF-α and IL-1β levels associated with EV treatment. In conclusion, the inflammation model provides an accessible tool to investigate the effects of blood products and EVs in the inflammatory context of OA.
Keywords:extracellular vesicles  inflammation  immunomodulation  coagulation  intercellular communication  blood products  osteoarthritis
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