Zhang Ao-Dan, Liu Heng-Chen, Zhang Ting-Ting, Li Xiang-Qi, Wu Yang, Guo Yu-Jun, Li Ru-Wei, Xu Bo, Jiang Zhi-Tao, Li Zhao-Zhu
Department of Pediatric Surgery, Women and Children's Hospital, School of Medicine, Xiamen University, Xiamen, China.
Department of Pediatric Surgery, Sixth Affiliated Hospital, Harbin Medical University, Harbin, China.
Am J Sports Med. 2025 Sep;53(11):2618-2632. doi: 10.1177/03635465251358465. Epub 2025 Aug 22.
Extracellular vesicles (EVs) from adipose-derived mesenchymal stem cells (ADSCs) play an important role in tendon healing and regeneration. However, the role of EVs in regulating tendon fibrosis during autophagy has not previously been reported.
To investigate the effect of EVs from ADSCs (ADSC-EVs) on the autophagy-mediated regulation of tendon fibrosis.
Controlled laboratory study.
We extracted ADSCs and tenocytes from Sprague-Dawley rats, isolated EVs, and verified their uptake by tenocyts tendon fibroblasts. To assess the effects of ADSC-EVs on tendon fibroblasts, we conducted an EdU (5-ethynyl-2'-deoxyuridine) assay, scratch assay, and transwell assay to evaluate cell proliferation and migration. The activation of autophagy, a fundamental function of eukaryotic cells, by ADSC-EVs was investigated through western blotting, transmission electron microscopy, and transfection with green fluorescent protein-red fluorescent protein-LC3B. Finally, an in vivo experiment was conducted using a patellar tendon healing model. Hematoxylin and eosin staining and biomechanical testing were performed to assess tendon healing.
In vitro, ADSC-EVs enhanced the proliferation and migration of tendon fibroblasts after uptake. In vivo, ADSC-EVs were mixed with a gelatin methacryloyl hydrogel, applied to the injured patellar tendon, and exposed to ultraviolet irradiation for coagulation. Biomechanical testing, immunohistochemistry, and hematoxylin and eosin staining confirmed that ADSC-EVs promoted effective tendon healing.
We demonstrated that ADSC-EVs reduced fibrosis during tendon healing by activating autophagy, thereby promoting high-quality healing.
Our findings confirm that ADSC-EVs can reduce fibrosis and inflammation during tendon healing, which may be a promising treatment approach to improve the quality of tendon healing. Therefore, ADSC-EVs have the potential to be used as cell-free biotherapeutics.
脂肪来源间充质干细胞（ADSCs）分泌的细胞外囊泡（EVs）在肌腱愈合和再生中发挥重要作用。然而，此前尚未有关于EVs在自噬过程中调节肌腱纤维化作用的报道。
研究ADSCs分泌的EVs（ADSC-EVs）对自噬介导的肌腱纤维化调节作用的影响。
对照实验室研究。
从Sprague-Dawley大鼠中提取ADSCs和肌腱细胞，分离EVs，并验证肌腱成纤维细胞对其摄取情况。为评估ADSC-EVs对肌腱成纤维细胞的影响，我们进行了EdU（5-乙炔基-2'-脱氧尿苷）检测、划痕试验和Transwell试验，以评估细胞增殖和迁移。通过蛋白质免疫印迹法、透射电子显微镜以及绿色荧光蛋白-红色荧光蛋白-LC3B转染，研究ADSC-EVs对自噬（真核细胞的一项基本功能）的激活作用。最后，使用髌腱愈合模型进行体内实验。进行苏木精-伊红染色和生物力学测试以评估肌腱愈合情况。
在体外，ADSC-EVs被摄取后可增强肌腱成纤维细胞的增殖和迁移。在体内，将ADSC-EVs与甲基丙烯酰化明胶水凝胶混合，应用于受伤的髌腱，并进行紫外线照射使其凝固。生物力学测试、免疫组织化学以及苏木精-伊红染色证实，ADSC-EVs促进了有效的肌腱愈合。
我们证明ADSC-EVs通过激活自噬减少肌腱愈合过程中的纤维化，从而促进高质量愈合。
我们的研究结果证实，ADSC-EVs可减少肌腱愈合过程中的纤维化和炎症，这可能是一种有前景的改善肌腱愈合质量的治疗方法。因此，ADSC-EVs有潜力用作无细胞生物治疗剂。
