Zou Mingrui, Wang Jingzhou, Shao Zhenxing
Department of Sports Medicine, Peking University Third Hospital, Institute of Sports Medicine of Peking University, Beijing 100191, China.
Beijing Key Laboratory of Sports Injuries, Engineering Research Center of Sports Trauma Treatment Technology and Devices, Ministry of Education, Beijing 100191, China.
J Funct Biomater. 2023 May 28;14(6):299. doi: 10.3390/jfb14060299.
Exosomes have been proven to play a positive role in tendon and tendon-bone healing. Here, we systematically review the literature to evaluate the efficacy of exosomes in tendon and tendon-bone healing. Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, a systematic and comprehensive review of the literature was performed on 21 January 2023. The electronic databases searched included Medline (through PubMed), Web of Science, Embase, Scopus, Cochrane Library and Ovid. In the end, a total of 1794 articles were systematically reviewed. Furthermore, a "snowball" search was also carried out. Finally, forty-six studies were included for analysis, with the total sample size being 1481 rats, 416 mice, 330 rabbits, 48 dogs, and 12 sheep. In these studies, exosomes promoted tendon and tendon-bone healing and displayed improved histological, biomechanical and morphological outcomes. Some studies also suggested the mechanism of exosomes in promoting tendon and tendon-bone healing, mainly through the following aspects: (1) suppressing inflammatory response and regulating macrophage polarization; (2) regulating gene expression, reshaping cell microenvironment and reconstructing extracellular matrix; (3) promoting angiogenesis. The risk of bias in the included studies was low on the whole. This systematic review provides evidence of the positive effect of exosomes on tendon and tendon-bone healing in preclinical studies. The unclear-to-low risk of bias highlights the significance of standardization of outcome reporting. It should be noted that the most suitable source, isolation methods, concentration and administration frequency of exosomes are still unknown. Additionally, few studies have used large animals as subjects. Further studies may be required on comparing the safety and efficacy of different treatment parameters in large animal models, which would be conducive to the design of clinical trials.
外泌体已被证明在肌腱和腱-骨愈合中发挥积极作用。在此，我们系统地回顾文献，以评估外泌体在肌腱和腱-骨愈合中的疗效。按照系统评价和Meta分析的首选报告项目指南，于2023年1月21日对文献进行了系统全面的回顾。检索的电子数据库包括Medline（通过PubMed）、科学网、Embase、Scopus、Cochrane图书馆和Ovid。最终，共系统回顾了1794篇文章。此外，还进行了“滚雪球”式检索。最后，纳入46项研究进行分析，总样本量为1481只大鼠、416只小鼠、330只兔子、48只狗和12只绵羊。在这些研究中，外泌体促进了肌腱和腱-骨愈合，并显示出组织学、生物力学和形态学结果的改善。一些研究还提出了外泌体促进肌腱和腱-骨愈合的机制，主要通过以下几个方面：（1）抑制炎症反应和调节巨噬细胞极化；（2）调节基因表达、重塑细胞微环境和重建细胞外基质；（3）促进血管生成。纳入研究的偏倚风险总体较低。本系统评价为外泌体在临床前研究中对肌腱和腱-骨愈合的积极作用提供了证据。偏倚风险不明确至低凸显了结果报告标准化的重要性。需要注意的是，外泌体最合适的来源、分离方法、浓度和给药频率仍不清楚。此外，很少有研究以大型动物为研究对象。可能需要进一步研究比较大型动物模型中不同治疗参数的安全性和有效性，这将有助于临床试验的设计。
