Mesenchymal stem cells (MSCs) and their produced exosomes have demonstrated inherent capabilities of inflammation‐guided targeting and inflammatory modulation, inspiring their potential applications as biologic agents for inflammatory treatments. However, the clinical applications of stem cell therapies are currently restricted by several challenges, and one of them is the mass production of stem cells to satisfy the therapeutic demands in the clinical bench. Herein, a production of human amnion‐derived MSCs (hMSCs) at a scale of over 1 × 109 cells per batch was reported using a three‐dimensional (3D) culture technology based on microcarriers coupled with a spinner bioreactor system. The present study revealed that this large‐scale production technology improved the inflammation‐guided migration and the inflammatory suppression of hMSCs, without altering their major properties as stem cells. Moreover, these large‐scale produced hMSCs showed an efficient treatment against the lipopolysaccharide (LPS)‐induced lung inflammation in mice models. Notably, exosomes collected from these large‐scale produced hMSCs were observed to inherit the efficient inflammatory suppression capability of hMSCs. The present study showed that 3D culture technology using microcarriers coupled with a spinner bioreactor system can be a promising strategy for the large‐scale expansion of hMSCs with improved anti‐inflammation capability, as well as their secreted exosomes.

中文翻译：

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大规模生产间充质干细胞及其外泌体，用于有效治疗肺部炎症

间充质干细胞（MSC）及其产生的外泌体已表现出炎症引导靶向和炎症调节的固有能力，激发了它们作为炎症治疗生物制剂的潜在应用。然而，干细胞疗法的临床应用目前受到一些挑战的限制，其中之一是干细胞的大规模生产以满足临床台的治疗需求。在此，人羊膜来源的 MSC (hMSC) 的生产规模超过 1 × 109使用基于微载体和旋转生物反应器系统的三维（3D）培养技术报告每批次的细胞数。本研究表明，这种大规模生产技术改善了 hMSC 的炎症引导迁移和炎症抑制，而不改变其作为干细胞的主要特性。此外，这些大规模生产的 hMSC 在小鼠模型中显示出对脂多糖（LPS）诱导的肺部炎症的有效治疗作用。值得注意的是，从这些大规模生产的 hMSC 中收集的外泌体被观察到继承了 hMSC 的有效炎症抑制能力。本研究表明，使用微载体与旋转生物反应器系统相结合的 3D 培养技术可以成为大规模扩增具有改善的抗炎能力的 hMSC 及其分泌的外泌体的有前途的策略。