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

来自 IFP-MSC 的 CD10 结合外泌体降解控制 OA 炎症和疼痛的 P 物质

• 批准号: 10524448
• 负责人: DIMITRIOS KOUROUPIS
• 金额: $ 16.89万
• 依托单位: UNIVERSITY OF MIAMI SCHOOL OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-07-18 至 2024-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10524448
• 关键词: Anatomy; Area; Arthralgia; Attenuated; Award; Biological; Biological Assay; Blood Platelets; Carrageenan; Cell physiology; Cells; Clinical; Clinical Data; Data; Degenerative polyarthritis; Development; Elderly; Event; Failure; Fatty acid glycerol esters; Fibrosis; General Population; Goals; Human; Immune; Immune system; In Vitro; Incidence; Infiltration; Inflammation; Inflammatory; Inflammatory Response; Intra-Articular Injections; Joints; Kaolin; Knee joint; Legal patent; Mediating; Mesenchymal Stem Cells; Modeling; Motivation; Neprilysin; Neuropeptides; Nociception; Outcome; Pain; Pain management; Pathway interactions; Phenotype; Protocols documentation; Public Health; Rattus; Replacement Arthroplasty; Reporting; Reproducibility; Research; Safety; Signal Transduction; Site; Small Interfering RNA; Source; Spinal; Spinal Ganglia; Standardization; Substance P; Synovial Membrane; Synovitis; Testing; Therapeutic; Therapeutic Effect; United States National Institutes of Health; Universities; articular cartilage; attenuation; base; cartilage degradation; chronic pain; clinical phenotype; disability; exosome; extracellular; gait examination; immunomodulatory therapies; immunoregulation; in vivo; inhibitor; joint inflammation; joint injury; knock-down; macrophage; microvesicles; novel; pain behavior; pain perception; palliative; paracrine; pre-clinical; stem cell exosomes; stem cells; therapeutic evaluation; translational study

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.

项目摘要 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， 等等），和局部炎症/免疫级联的共同激活。滑膜炎/髌下脂肪垫（IFP） 纤维化参与OA，P物质（SP）神经肽介导疼痛感知和局部疼痛， 免疫/炎症反应。富含CD 10的IFP来源的间充质干细胞（IFP-MSC）诱导 体外和体内SP降解显著逆转滑膜炎/IFP纤维化和衰减关节软骨 降解IFP-MSC上清液通过释放CD 10结合的外来体降解SP 细胞外微泡。该项目旨在产生具有不同CD 10水平的外泌体（未分级-未分级）。 、CD 10高-、CD 10低-和siCD 10-结合的外来体）从免疫表型分选的IFP-MSC中分离， 符合法规的做法。将测试产生的外泌体组的SP降解作用 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。