Tendon stem cells (TSCs) have been reported to hold promises for tendon repair and regeneration. However, less is known about the effects of exosomes derived from TSCs. Therefore, we aimed to clarify the healing effects of TSC-derived exosomes (TSC-Exos) on tendon injury. The Achilles tendons of Sprague-Dawley male rats were used for primary culture of TSCs and tenocytes, and exosomes were isolated from TSCs. The proliferation of tenocytes induced by TSC-Exos was analyzed using an EdU assay; cell migration was measured by cell scratch and transwell assays. We used western blot to analyze the role of the PI3K/AKT and MAPK/ERK1/2 signaling pathways. In vivo, Achilles tendon injury models were created in Sprague-Dawley rats. Rats (n = 54) were then randomly assigned to three groups: the TSC-Exos group, the GelMA group, and the control group. We used immunofluorescence to detect changes in the expression of inflammatory and apoptotic markers at 1 week after surgery. Histology and changes in expression of extracellular matrix (ECM)-related indices were assessed by hematoxylin-eosin (H&E) staining and immunohistochemistry at 2 and 8 weeks. The collagen fiber diameter of the healing tendon was analyzed at 8 weeks by transmission electron microscopy (TEM). TSC-Exos were taken up by tenocytes, which promoted the proliferation and migration of cells in a dose-dependent manner; this process may depend on the activation of the PI3K/AKT and MAPK/ERK1/2 signaling pathways. At 1 week after surgery, we found that inflammation and apoptosis were significantly suppressed by TSC-Exos. At 2 and 8 weeks, tendons treated with TSC-Exos showed more continuous and regular arrangement in contrast to disorganized tendons in the GelMA and control groups, and TSC-Exos may help regulate ECM balance and inhibited scar formation. Further, at 8 weeks, the TSC-Exos group had a larger diameter of collagen compared to the control group. Our data suggest that TSC-Exos could promote high-quality healing of injured tendon, which may be a promising therapeutic approach for tendon injury.

中文翻译：

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肌腱干细胞衍生的外来体可调节炎症并促进受损肌腱的高质量愈合。

肌腱干细胞（TSC）据报道有望进行肌腱修复和再生。但是，关于源自TSC的外泌体的作用了解甚少。因此，我们旨在阐明TSC衍生的囊泡（TSC-Exos）对肌腱损伤的愈合作用。将Sprague-Dawley雄性大鼠的跟腱用于TSC和肌腱细胞的原代培养，并从TSC中分离出外泌体。使用EdU分析法分析了由TSC-Exos诱导的肌腱细胞增殖。细胞迁移通过细胞划痕和transwell测定法测量。我们使用蛋白质印迹来分析PI3K / AKT和MAPK / ERK1 / 2信号通路的作用。在体内，在Sprague-Dawley大鼠中创建了跟腱损伤模型。然后将大鼠（n = 54）随机分为三组：TSC-Exos组，GelMA组和对照组。我们在手术后1周使用免疫荧光检测炎症和凋亡标记物表达的变化。在第2周和第8周通过苏木精曙红（H＆E）染色和免疫组化评估组织学和细胞外基质（ECM）相关指标表达的变化。通过透射电子显微镜（TEM）在8周时分析愈合肌腱的胶原纤维直径。TSC-Exos被肌腱细胞吸收，以剂量依赖的方式促进细胞的增殖和迁移。这个过程可能取决于PI3K / AKT和MAPK / ERK1 / 2信号通路的激活。术后1周，我们发现TSC-Exos显着抑制了炎症和细胞凋亡。在第2周和第8周，与GelMA和对照组的混乱的肌腱相反，经TSC-Exos治疗的肌腱表现出更连续和规则的排列，TSC-Exos可能有助于调节ECM平衡并抑制疤痕形成。此外，与对照组相比，在第8周时，TSC-Exos组的胶原蛋白直径更大。我们的数据表明，TSC-Exos可以促进受伤肌腱的高质量愈合，这可能是一种有希望的肌腱损伤治疗方法。