Mesenchymal stem cells derived exosomes and microparticles protect cartilage and bone from degradation in osteoarthritis.
Mesenchymal stem cells derived exosomes and microparticles protect cartilage and bone from degradation in osteoarthritis.
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DOI：
10.1038/s41598-017-15376-8
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发表时间：
2017-11-24
影响因子：
4.6
通讯作者：
Noël D
中科院分区：
文献类型：
--
作者：
Cosenza S;Ruiz M;Toupet K;Jorgensen C;Noël D
间充质干细胞或基质细胞（MSC）在骨关节炎（OA）的临床前模型中发挥软骨保护作用。它们的大多数治疗作用是通过可溶性介质介导的，可溶性介质可以在细胞外囊泡（EV）内传递。本研究的目的是比较外泌体（Exos）或微泡/微粒（MP）在OA中的各自作用。通过差速离心从小鼠骨髓BM-MSC中分离MP和Exos。评估MP或Exos对OA样鼠软骨细胞的作用，并通过RT-qPCR定量软骨保护。在OA样软骨细胞中，BM-MSC衍生的MP和Exos可以恢复软骨细胞标志物（II型胶原、聚集蛋白聚糖）的表达，同时抑制分解代谢（MMP-13、ADAMTS 5）和炎性（iNOS）标志物。Exos和MP也显示出保护软骨细胞免于凋亡并抑制巨噬细胞活化。在体内，在胶原酶诱导的OA（CIOA）模型中注射Exos或MP，并通过µCT和共聚焦激光显微镜进行关节的组织形态计量学分析。BM-MSC、MP和Exos同样保护小鼠免受关节损伤。总之，MP和Exos在体外发挥了相似的软骨保护和抗炎功能，并在体内保护小鼠免于发生OA，这表明Exos或MP再现了BM-MSC的主要治疗作用。
Mesenchymal stem or stromal cells (MSCs) exert chondroprotective effects in preclinical models of osteoarthritis (OA). Most of their therapeutic effects are mediated via soluble mediators, which can be conveyed within extracellular vesicles (EVs). The objective of the study was to compare the respective role of exosomes (Exos) or microvesicles/microparticles (MPs) in OA. MPs and Exos were isolated from bone marrow murine BM-MSCs through differential centrifugation. Effect of MPs or Exos was evaluated on OA-like murine chondrocytes and chondroprotection was quantified by RT-qPCR. In OA-like chondrocytes, BM-MSC-derived MPs and Exos could reinduce the expression of chondrocyte markers (type II collagen, aggrecan) while inhibiting catabolic (MMP-13, ADAMTS5) and inflammatory (iNOS) markers. Exos and MPs were also shown to protect chondrocytes from apoptosis and to inhibit macrophage activation. In vivo, Exos or MPs were injected in the collagenase-induced OA (CIOA) model and histomorphometric analyses of joints were performed by µCT and confocal laser microscopy. BM-MSCs, MPs and Exos equally protected mice from joint damage. In conclusion, MPs and Exos exerted similar chondroprotective and anti-inflammatory function in vitro and protected mice from developing OA in vivo, suggesting that either Exos or MPs reproduced the main therapeutic effect of BM-MSCs.
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影响因子：
3.7
作者：
Toupet K;Maumus M;Luz-Crawford P;Lombardo E;Lopez-Belmonte J;van Lent P;Garin MI;van den Berg W;Dalemans W;Jorgensen C;Noël D
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通讯作者：
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影响因子：
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