Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, China; Hunan Provincical Key Laboratory of Neurorestoratology, The Second Affiliated Hospital, Hunan Normal University, Changsha, 410003, China; First Clinical Department of Changsha Medical University, The 1501 Leifeng Road in Wangcheng District, Changsha, 410219, China.
Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, China.
Biochem Biophys Res Commun. 2024 Jul 12;717:150021. doi: 10.1016/j.bbrc.2024.150021. Epub 2024 Apr 27.
Mesenchymal stem cells (MSCs) are ubiquitous multipotent cells exhibiting significant therapeutic potential for various diseases. It is generally accepted that clinical application requires massive expansion of MSCs, which is often accompanied by the occurrence of replicative senescence. Additionally, senescent MSCs exhibit significantly reduced proliferation, differentiation, and therapeutic potential. The scale-up of MSCs production and cellular senescence are major challenges for translational applications. This study first collected extracellular vesicles (EVs) from gingival MSCs (GMSCs) under hypoxia preconditioning combined with 3D dynamic culture (obtained EVs designed as H-3D-EVs). Subsequently, we further explored the effects and mechanisms of H-3D-EVs on aging-GMSCs. The results showed that H-3D-EVs improved the proliferation ability and cell activity of aging-GMSCs, and ameliorated their senescence. mRNA sequencing reveals transcriptomic changes in aging-GMSCs. It was found that H-3D-EVs up-regulated genes related to mitochondrial dynamics, cell cycle, and DNA repair, while down-regulated aging-related genes. Furthermore, we verified that H-3D-EVs corrected the mitochondrial dysfunction of aging-GMSCs by improving mitochondrial dynamics. In summary, this study provides a promising strategy for improving the culture methods of GMSCs and avoiding its senescence in large-scale production.
间充质干细胞（MSCs）是普遍存在的多能细胞，对各种疾病具有显著的治疗潜力。人们普遍认为，临床应用需要大量扩增 MSCs，而这通常伴随着复制性衰老的发生。此外，衰老的 MSCs表现出明显降低的增殖、分化和治疗潜力。MSCs 生产的扩大和细胞衰老的发生是转化应用的主要挑战。本研究首先从缺氧预处理结合 3D 动态培养的牙龈间充质干细胞（GMSCs）中收集细胞外囊泡（EVs）（获得的 EVs 设计为 H-3D-EVs）。随后，我们进一步探讨了 H-3D-EVs 对衰老-GMSCs 的作用和机制。结果表明，H-3D-EVs 提高了衰老-GMSCs 的增殖能力和细胞活性，并改善了它们的衰老状态。mRNA 测序揭示了衰老-GMSCs 的转录组变化。研究发现，H-3D-EVs 上调了与线粒体动力学、细胞周期和 DNA 修复相关的基因，同时下调了与衰老相关的基因。此外，我们验证了 H-3D-EVs 通过改善线粒体动力学纠正了衰老-GMSCs 的线粒体功能障碍。综上所述，本研究为改善 GMSCs 的培养方法并避免其在大规模生产中的衰老提供了一种有前景的策略。
