Background:The self-repair ability after meniscal tears is poor, leading to the development of posttraumatic osteoarthritis. Promoting the repair of meniscal injuries remains a great challenge, especially in the avascular region.Hypothesis:Local delivery of skeletal stem cell (SSC)–derived exosomes (SSC-Exos) would promote meniscal healing and prevent secondary osteoarthritis progression.Study Design:Controlled laboratory study.Methods:SSCs were isolated from bone marrow and exosomes were extracted via ultracentrifugation. The cell migration capabilities after incubation with exosomes were validated through in vitro cell culture. Full-thickness longitudinal medial meniscal tears were performed in the avascular region of 40 male Sprague-Dawley rats and 20 male New Zealand White rabbits, which were randomly divided into 2 groups: group treated with phosphate-buffered saline (GCON) and group treated with exosomes (GExosome). The effects of these treatments on meniscal healing and secondary osteoarthritis were evaluated by gross inspection, biomechanical testing, and histological assessment. RNA sequencing of in vitro cell cultures was performed to explore the underlying mechanisms.Results:Exosomes were successfully extracted and identified. These exosomes significantly promoted cell migration capabilities in vitro ( P < .01). The GExosome exhibited greater cell proliferation and tissue regeneration with type 2 collagen secretion, and a significantly higher meniscal repair score than that of the GCON at 8 weeks postoperatively ( P < .05). In contrast to the degenerative changes in both the meniscus and articular cartilage of the GCON, meniscal tissue in the GExosome exhibited restoration of normal morphology with a smooth and glossy white surface and better mechanical strength at 8 weeks after meniscal repair. Both degeneration scores and synovitis scores were significantly higher in the GCON than in the GExosome ( P < .05). Compared with the GCON, the expression of key genes related to cell migration, such as the chemokine family, was enhanced by exosome injection, leading to an upregulation of extracellular matrix expression while downregulating the expression of inflammation-related genes such as CD68 and the matrix metalloproteinase family.Conclusion:The administration of SSC-Exos effectively promoted meniscal healing in the avascular region and ameliorated secondary osteoarthritis. The effect might be attributed to inflammation modulation, promotion of cell migration, and secretion of extracellular matrix components.Clinical Relevance:Injection of SSC-Exos represents a promising therapeutic option for promoting meniscal healing in the avascular region.

中文翻译：

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骨骼干细胞衍生的外泌体促进半月板撕裂愈合并改善继发性骨关节炎


背景：半月板撕裂后自我修复能力差，导致创伤后骨关节炎的发生。促进半月板损伤的修复仍然是一个巨大的挑战，特别是在无血管区域。假设：局部递送骨骼干细胞（SSC）衍生的外泌体（SSC-Exos）将促进半月板愈合并预防继发性骨关节炎进展。研究设计：对照方法：从骨髓中分离SSC，并通过超速离心提取外泌体。通过体外细胞培养验证了与外泌体孵育后的细胞迁移能力。 40只雄性Sprague-Dawley大鼠和20只雄性新西兰白兔的无血管区进行全层纵向内侧半月板撕裂，随机分为2组：磷酸盐缓冲盐水组（G组）康）和用外泌体治疗的组（G外泌体）。通过肉眼检查、生物力学测试和组织学评估来评估这些治疗对半月板愈合和继发性骨关节炎的影响。对体外细胞培养物进行RNA测序，探讨其潜在机制。结果：成功提取并鉴定了外泌体。这些外泌体显着促进了细胞的体外迁移能力（P < .01）。 G外泌体与 G 组相比，G 组表现出更大的细胞增殖和组织再生以及 2 型胶原分泌，并且半月板修复评分显着更高康术后 8 周 ( P < .05)。 与 G 的半月板和关节软骨的退行性变化相反康，G中的半月板组织外泌体半月板修复后 8 周，表现出正常形态的恢复，具有光滑、有光泽的白色表面和更好的机械强度。 G 组退化评分和滑膜炎评分均显着较高康比在G外泌体( P < .05)。与G相比康外泌体注射增强了趋化因子家族等与细胞迁移相关的关键基因的表达，导致细胞外基质表达上调，同时下调了CD68和基质金属蛋白酶家族等炎症相关基因的表达。结论：SSC-Exos 的施用有效促进无血管区域的半月板愈合并改善继发性骨关节炎。该效应可能归因于炎症调节、促进细胞迁移和细胞外基质成分的分泌。临床相关性：注射 SSC-Exos 是促进无血管区域半月板愈合的一种有前景的治疗选择。