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

项目总结 骨关节炎(OA)的“临床表型”具有相似的临床终点(疼痛、僵硬、关节损伤、 等)，以及局部炎症/免疫级联反应的共同激活。滑膜炎/髌下脂肪垫(IFP) 纤维化参与骨性关节炎，P物质(SP)神经肽介导痛觉和局部 免疫/炎症反应。富含CD10的IFP来源的间充质干细胞诱导 SP在体内和体外的降解显著逆转滑膜炎/IFP纤维化和关节软骨的减弱 退化。IFP-MSC上清液通过释放CD10结合的外切体降解SP 细胞外的微泡。该项目旨在生成具有不同CD10水平的外体(未分级- 、CD10High、CD10Low和siCD10结合的外切体)从免疫表型分选的IFP-MSC 符合监管规定的做法。生成的外切体组将被测试其SP降解效果 在体外和体内，以及它们同时靶向滑膜炎/IFP纤维化的治疗效果 减轻关节疼痛和体内AC降解。

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.