CD10-bound Exosomes from IFP-MSC Degrade Substance P Controlling OA Inflammation and Pain

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PROJECT SUMMARY Osteoarthritis (OA) ‘clinical phenotypes’ have similar clinical end-points (pain, stiffness, joint damage, etc.), and a common activation of local inflammatory/immune cascades. Synovitis/infrapatellar fat pad (IFP) fibrosis participate in OA, with Substance P (SP) neuropeptide mediating pain perception and local immune/inflammatory responses. IFP-derived Mesenchymal Stem Cells (IFP-MSC) enriched for CD10 induce SP degradation in vitro and in vivo significantly reversing synovitis/IFP fibrosis and attenuating articular cartilage degradation. IFP-MSC supernatant comparably degrades SP via the release of CD10-bound exosomes extracellular microvesicles. This project aims at generating exosomes with varying CD10 levels (Unfractionated- , CD10High-, CD10Low-, and siCD10-bound exosomes) from immunophenotypically sorted IFP-MSC under regulatory-compliant practices. The generated exosomes groups will be tested for their SP degradation effects in vitro and in vivo, and their therapeutic effects to simultaneously target synovitis/IFP fibrosis together with attenuation of joint pain and AC degradation in vivo.