Freshage Research Group, Department of Physiology, Faculty of Medicine, University of Valencia, Centro de Investigación Biomédica en Red Fragilidad y Envejecimiento Saludable-Instituto de Salud Carlos III (CIBERFES-ISCIII), INCLIVA, Valencia, 46010, Spain.
Freshage Research Group, Department of Physiology, Faculty of Medicine, University of Valencia, Centro de Investigación Biomédica en Red Fragilidad y Envejecimiento Saludable-Instituto de Salud Carlos III (CIBERFES-ISCIII), INCLIVA, Valencia, 46010, Spain; Department of Cardiology, Hospital Universitari I Politècnic La Fe, 46026, Valencia, Spain.
Redox Biol. 2023 Jun;62:102668. doi: 10.1016/j.redox.2023.102668. Epub 2023 Mar 21.
Extracellular vesicles' biogenesis, shedding, and uptake are redox-sensitive. Indeed, oxidative stress conditions influence extracellular vesicles' release and content, which can modulate the redox status of the receiving cells. In this study, we aimed to assess the effect of extracellular vesicles from human dental pulp stem cells cultured under 21% O (senescent stem cells) on human dental pulp stem cells cultured under 3% O (young stem cells). Extracellular vesicles were isolated by ultracentrifugation from senescent stem cells and prepared for the treatment of young stem cells at a final concentration of 10 μg/mL. Cells were analyzed for antioxidant gene expression, mitochondrial bioenergetic parameters, ROS production, culture kinetics, and apoptosis. The results show that extracellular vesicles from senescent stem cells induce overexpression of antioxidant genes (MnSOD, CAT, and GPx) in young stem cells, which show an increased non-mitochondrial oxygen consumption, accompanied by reduced maximal respiration and spare respiratory capacity without altering mitochondrial membrane potential. This is accompanied by improved cell proliferation, viability, and migration rates and a reduction of apoptosis. In conclusion, extracellular vesicles from senescent stem cells trigger an adaptive response in young stem cells which improves their antioxidant defenses and their proliferation, migration, and survival rates. This suggests that extracellular vesicles can modulate the cells' microenvironment and the balance between proliferation and senescence.
细胞外囊泡的发生、脱落和摄取对氧化还原敏感。事实上，氧化应激条件会影响细胞外囊泡的释放和内容物，从而调节接受细胞的氧化还原状态。在这项研究中，我们旨在评估在 21%氧气下培养的人牙髓干细胞（衰老干细胞）的细胞外囊泡对在 3%氧气下培养的人牙髓干细胞（年轻干细胞）的影响。通过超速离心从衰老干细胞中分离出外泌体，并在最终浓度为 10μg/ml 的条件下准备用于处理年轻干细胞。分析细胞的抗氧化基因表达、线粒体生物能参数、ROS 产生、培养动力学和细胞凋亡。结果表明，衰老干细胞的细胞外囊泡诱导年轻干细胞中抗氧化基因（MnSOD、CAT 和 GPx）的过度表达，表现为非线粒体耗氧量增加，同时最大呼吸和备用呼吸能力降低，而线粒体膜电位不变。这伴随着细胞增殖、活力和迁移率的提高以及细胞凋亡的减少。总之，衰老干细胞的细胞外囊泡在年轻干细胞中引发适应性反应，增强其抗氧化防御能力以及增殖、迁移和存活率。这表明细胞外囊泡可以调节细胞的微环境以及增殖和衰老之间的平衡。
