Animal and clinical studies have shown that mesenchymal stem cells (MSCs) play an important role in cartilage repair. The therapeutic effect of mesenchymal stem cells based therapies has been increasingly demonstrated to exosome-mediated paracrine secretion. Here, we investigated the cellular processes and mechanism of exosomes produced by conventional 2D culture (2D-Exos) and exosomes produced from 3D culture (3D-Exos) of umbilical MSCs (U-MSCs) in a hollow-fiber bioreactor for the treatment of cartilage repair. We found that the yield of 3D-Exos was 7.5-fold higher than that of 2D-Exos. The in vitro experiments indicated that both 2D-Exos and 3D-Exos can stimulate chondrocyte proliferation, migration, and matrix synthesis, and inhibit apoptosis, with 3D-Exos exerting a stronger effect than 2D-Exos. This effect was partly attributed to the activation of transforming growth factor beta 1 and Smad2/3 signaling. The injection of 2D-Exos and 3D-Exos showed enhanced gross appearance and attenuated cartilage defect; however, 3D-Exos showed a superior therapeutic effect than 2D-Exos. In summary, our study provides novel insights into the chondroprotective effects of exosomes produced from 3D culture of U-MSCs in a hollow-fiber bioreactor. Because of its promising biological function and high yield, 3D-Exos may become a promising therapeutic method for the treatment of cartilage defects.

中文翻译：

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在空心纤维生物反应器中由脐带间充质干细胞的3D培养产生的外泌体显示出改善的骨软骨再生活性。

动物和临床研究表明，间充质干细胞（MSC）在软骨修复中起重要作用。基于间充质干细胞的疗法的治疗作用已被越来越多地证明为外泌体介导的旁分泌。在这里，我们研究了在空心纤维生物反应器中，常规2D培养物（2D-Exos）和脐带MSC（U-MSC）的3D培养物（3D-Exos）产生的外泌体的细胞过程和机理。软骨修复。我们发现3D-Exos的产量是2D-Exos的7.5倍。体外实验表明2D-Exos和3D-Exos均可刺激软骨细胞增殖，迁移和基质合成，并抑制细胞凋亡，其中3D-Exos的作用要强于2D-Exos。该作用部分归因于转化生长因子β1和Smad2 / 3信号的激活。2D-Exos和3D-Exos的注射显示出增强的肉眼外观和减弱的软骨缺损。然而，3D-Exos显示出比2D-Exos更好的治疗效果。总而言之，我们的研究为中空纤维生物反应器中U-MSC的3D培养产生的外泌体的软骨保护作用提供了新的见解。由于其有希望的生物学功能和高产率，3D-Exos可能成为治疗软骨缺损的有前途的治疗方法。我们的研究为中空纤维生物反应器中U-MSC的3D培养产生的外来体的软骨保护作用提供了新颖的见解。由于其有希望的生物学功能和高产率，3D-Exos可能成为治疗软骨缺损的有前途的治疗方法。我们的研究为中空纤维生物反应器中U-MSC的3D培养产生的外来体的软骨保护作用提供了新颖的见解。由于其有希望的生物学功能和高产率，3D-Exos可能成为治疗软骨缺损的有前途的治疗方法。