Exosomes derived from umbilical cord mesenchymal stem cells protect cartilage and regulate the polarization of macrophages in osteoarthritis.
Exosomes derived from umbilical cord mesenchymal stem cells protect cartilage and regulate the polarization of macrophages in osteoarthritis.
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DOI：
10.21037/atm-22-3912
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发表时间：
2022-09
影响因子：
--
通讯作者：
Li, Yulin
中科院分区：
文献类型：
--
作者：
Li, Pengdong;Lv, Shuang;Jiang, Wenyue;Si, Lihui;Liao, Baojian;Zhao, Guifang;Xu, Ziran;Wang, Lina;Zhang, Jia;Wu, Haitao;Peng, Qian;Li, Zhaohui;Qi, Ling;Chi, Guangfan;Li, Yulin
关键词：
骨关节炎（OA）是最常见的关节疾病之一，也是全球主要的公共卫生问题。间充质干细胞（MSC）因其旁分泌营养因子而被广泛用于治疗OA，外泌体可能在这种现象中发挥重要作用。在这里，我们研究了来自人脐带来源的MSC（hUC-MSC-Exos）的外泌体在缓解OA中的潜力。使用超离心从hUC-MSC条件培养基收获hUC-MSC-Exos。关节内注射hUC-MSC-Exos治疗关节炎大鼠。采用HE染色、番红-O染色、快绿色染色及免疫组化方法观察hUC-MSCs-Exos对骨关节软骨的修复作用。进一步进行体外实验以验证其治疗效果。使用细胞计数试剂盒-8、EdU-555细胞增殖试剂盒和transwell测定来评估hUC-MSC-Exos对人软骨细胞增殖和迁移的影响。Annexin V-FITC/PI染色观察exosomes对软骨细胞凋亡的影响。使用白细胞介素1 β（IL-1β）处理的人关节软骨细胞体外模型评价外来体的作用，分析涉及使用定量实时聚合酶链反应（qRT-PCR）、免疫荧光和蛋白质印迹。通过qRT-PCR和免疫荧光在单核细胞系Tohoku Hospital Pediatrics-1（THP-1）中检查hUC-MSC-Exos在巨噬细胞极化中的作用。结果显示，hUC-MSCs-Exos预防了大鼠OA模型中膝关节软骨的严重损伤。我们证实了hUC-MSC-Exos在促进软骨细胞增殖和迁移以及抑制软骨细胞凋亡方面的高功效。hUC-MSCs-Exos能逆转IL-1β诱导的软骨细胞损伤，并能调节巨噬细胞的极化。hUC-MSC-Exos有可能用作OA的治疗策略。
Osteoarthritis (OA) is one of the most common joint diseases and a major global public health concern. Mesenchymal stem cells (MSCs) have been widely used for the treatment of OA owing to their paracrine secretion of trophic factors, a phenomenon in which exosomes may play a major role. Here, we investigate the potential of exosomes from human umbilical cord-derived MSCs (hUC-MSCs-Exos) in alleviating OA. The hUC-MSCs-Exos were harvested from hUC-MSC-conditioned medium using ultracentrifugation. Rats with surgically-induced OA were intra-articularly injected with hUC-MSCs-Exos. The effect of hUC-MSCs-Exos in repairing osteoarticular cartilage was assessed using hematoxylin and eosin (HE) staining, safranin-O and fast green staining and immunohistochemistry. The in vitro experiments were further carried out to verify the therapeutic effect. The effects of hUC-MSCs-Exos on the proliferation and migration of human chondrocytes were evaluated using the cell counting kit-8, EdU-555 cell proliferation kit, and transwell assays. Annexin V-FITC/PI staining were used to evaluate the effect of exosomes on chondrocyte apoptosis. An in vitro model of human articular chondrocytes treated with interleukin 1 beta (IL-1β) was used to evaluate the effects of exosomes, analyses involved using quantitative real-time polymerase chain reaction (qRT-PCR), immunofluorescence, and western blotting. The role of hUC-MSCs-Exos in macrophage polarization was examined in the monocyte cell line, Tohoku Hospital Pediatrics-1 (THP-1) by qRT-PCR and immunofluorescence. The results showed that hUC-MSCs-Exos prevented severe damage to the knee articular cartilage in the rat OA model. We confirmed the high efficacy of hUC-MSCs-Exos in promoting chondrocyte proliferation and migration and inhibiting chondrocyte apoptosis. Additionally, hUC-MSCs-Exos could reverse IL-1β-induced injury of chondrocytes and regulate the polarization of macrophages in vitro. There is potential for hUC-MSCs-Exos to be used as a treatment strategy for OA.
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DOI：
10.1126/science.aau6977
发表时间：
2020-02-07
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Kalluri R;LeBleu VS
通讯作者：
LeBleu VS
影响因子：
4.6
作者：
Cosenza S;Ruiz M;Toupet K;Jorgensen C;Noël D
通讯作者：
Noël D
有证据表明 miR-146a 通过抑制 Notch1、IL-6 和 IL-1 介导的分解代谢来减轻衰老和创伤引起的骨关节炎
影响因子：
7.8
作者：
Guan YJ;Li J;Yang X;Du S;Ding J;Gao Y;Zhang Y;Yang K;Chen Q
通讯作者：
Chen Q
影响因子：
3.7
作者：
Lankford KL;Arroyo EJ;Nazimek K;Bryniarski K;Askenase PW;Kocsis JD
通讯作者：
Kocsis JD
源自过表达 miR-92a-3p 的人间充质干细胞的外泌体通过靶向 WNT5A 增强软骨形成并抑制软骨降解。
影响因子：
7.5
作者：
Mao G;Zhang Z;Hu S;Zhang Z;Chang Z;Huang Z;Liao W;Kang Y
通讯作者：
Kang Y