Clinical and animal studies have demonstrated efficacy of mesenchymal stem/stromal cells (MSCs) in cartilage repair. Although MSCs were originally predicated to mediate tissue repair through cellular differentiation and cell replacement, it is now recognized that MSCs exert most of their paracrine effects on tissue repair through the release of extracellular vesicles (EVs). In particular, 50–200 nm small EVs that also include exosomes carry a rich cargo of lipids, nucleic acids, and proteins, and have been reported to be therapeutically efficacious in various disease indications, including osteochondral injuries and osteoarthritis (OA). This systematic review aimed to assess the preclinical studies that used MSC exosomes for cartilage repair. Following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines, PubMed and Cochrane Library databases were searched for relevant controlled preclinical animal studies. A total of 13 studies were identified, with the total sample size being 434. This included 378 (87.1%) mice or rats and 56 (12.9%) rabbits. According to Systematic Review Centre for Laboratory Animal Experimentation risk of bias assessment, all the studies presented with unclear-to-low risk in bias. In general, MSC exosomes were found to be efficacious in promoting repair and regeneration of osteochondral defects and alleviating OA degeneration. In most studies, exosome-treated animals displayed increased cellular proliferation, enhanced matrix deposition, and improved histological scores. Having assessed the relevant preclinical animal studies reported to date, this systematic review shows the therapeutic benefit of MSC exosome therapy in cartilage repair. Standardization of animal models and outcome measurements would be needed to facilitate more robust analysis and improve the validity of the results in future studies.

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用于软骨再生的间充质干细胞外泌体：临床前体内研究的系统评价

临床和动物研究已经证明了间充质干/基质细胞 (MSC) 在软骨修复中的功效。尽管 MSC 最初被认为通过细胞分化和细胞替代介导组织修复，但现在人们认识到 MSC 通过释放细胞外囊泡 (EV) 对组织修复发挥大部分旁分泌作用。特别是，还包括外泌体的 50-200 nm 小 EVs 携带丰富的脂质、核酸和蛋白质，据报道在各种疾病适应症中具有治疗效果，包括骨软骨损伤和骨关节炎 (OA)。本系统综述旨在评估使用 MSC 外泌体进行软骨修复的临床前研究。遵循系统评价和 Meta 分析的首选报告项目指南，在 PubMed 和 Cochrane 图书馆数据库中搜索了相关的受控临床前动物研究。共确定了 13 项研究，总样本量为 434。其中包括 378 (87.1%) 只小鼠或大鼠和 56 (12.9%) 只兔子。根据实验动物实验系统评价中心的偏倚风险评估，所有研究的偏倚风险从不清楚到低。总的来说，MSC外泌体被发现在促进骨软骨缺损的修复和再生以及缓解OA退化方面是有效的。在大多数研究中，外泌体处理的动物表现出细胞增殖增加、基质沉积增强和组织学评分改善。评估了迄今为止报告的相关临床前动物研究，该系统评价显示了 MSC 外泌体疗法在软骨修复中的治疗益处。需要对动物模型和结果测量进行标准化，以促进更可靠的分析并提高未来研究结果的有效性。