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

基本信息

批准号：
10667619
负责人：
DIMITRIOS KOUROUPIS
金额：
$ 20.26万
依托单位：
UNIVERSITY OF MIAMI SCHOOL OF MEDICINE
依托单位国家：
美国
项目类别：
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/10667619
关键词：
Anatomy Area Arthralgia Attenuated Award Binding Biological Biological Assay Blood Platelets Carrageenan Cell physiology Cells Clinical Data Degenerative polyarthritis Development Elderly Engraftment Event Failure Fatty acid glycerol esters Fibrosis Formulation General Population Goals Human Immune Immune system Immunophenotyping In Vitro Incidence Inflammation Inflammatory Inflammatory Response Intra-Articular Injections Joints Kaolin Knee joint Legal patent Macrophage Mediating Mesenchymal Stem Cells Modeling Motivation Neprilysin Neuropeptides Nociception Outcome Pain Pain Measurement Pain management Pathway interactions Phenotype Population Protocols documentation Public Health Rattus Replacement Arthroplasty Reporting Reproducibility Research Safety Signal Transduction Site Small Interfering RNA Sorting Source Spinal Spinal Ganglia Standardization Substance P Synovial Membrane Synovitis Testing Therapeutic Therapeutic Effect United States National Institutes of Health Universities Vertebral column articular cartilage attenuation cartilage degradation chronic pain clinical phenotype disability exosome extracellular gait examination immune cell infiltrate immunomodulatory therapies immunoregulation in vivo inhibitor joint inflammation joint injury knock-down manufacture microvesicles novel pain behavior pain perception palliative paracrine pre-clinical stem cell exosomes stem cells therapeutic evaluation translational study transmission process vesicular release

项目摘要

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）“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/免疫级联反应的常见激活。滑膜炎/frapatillar脂肪垫（IFP）纤维化参与OA，物质P（SP）神经肽介导疼痛感和局部免疫/炎症反应。 IFP衍生的间充质干细胞（IFP-MSC）富含CD10的影响 SP在体外和体内降解显着逆转滑膜炎/IFP纤维化和衰减关节软骨降解。 IFP-MSC上清液可通过释放CD10结合外泌体降低SP 细胞外微泡。该项目旨在生成具有不同CD10水平的外泌体（未分流 - ，CD10-HIGH-，CD10LOW-和SICD10结合外泌体）从免疫表达中分类的IFP-MSC。符合法规的实践。生成的外泌体组将测试其SP降解效应体外和体内，以及它们仅针对滑膜炎/IFP纤维化的治疗作用关节疼痛和体内交流降解的衰减。