Therapeutic efficacy of hiMSC-derived Extracellular Vesicles from Serum-containing and Xeno-free media for osteoarthritis treatment

Abstract

BackgroundExtracellular vesicles derived from human induced mesenchymal stromal cells (hiEVs) constitute a promising cell-free therapeutic option for osteoarthritis. To allow translation to the clinic we evaluated the therapeutic effects of hiEVs for osteoarthritis treatment. Specifically, we assessed the efficacy of hiEVs collected from serum-containing and serum-free, PurStem (PS), media in an OA mice model. MethodshiEVs were administered with or without hydrogel via intra-articular (i.a.) injection in a destabilization of the medial meniscus (DMM) mouse model. Fluorescence imaging was used to monitor the retention of IR780-labeled hiEVs in the joint cavity. The therapeutic effects were evaluated by analyzing damage scores as well as catabolic and anabolic markers, including Mmp13 and Col2 expression, in joint tissues. ResultsFluorescence imaging confirmed that hiEVs remained localized at the injection site without systemic migration. HiEVs demonstrated significant protective effects against joint tissue degeneration in the DMM mouse OA model, as evidenced by reduced damage scores, decreased Mmp13 expression, and increased anabolic processes (Col2 expression). The hydrogel alone also exerted beneficial therapeutic effects, including reduced damage scores, increased Col2 expression, and reduced Mmp13 levels; however, these effects were notably smaller than those achieved with hiEV treatment while it was independent of the medium used for hiEV collection. ConclusionsTogether, our findings demonstrate that hiEVs from xeno-free conditions effectively prevent cartilage degradation and promote its repair. This paves the way for future clinical translation of hiEV-based therapies as a safe, scalable, and effective approach to treat osteoarthritis.