Clinic for Conservative Dentistry and Periodontology, School of Dental Medicine, Christian-Albrechts-University, 24105 Kiel, Germany.
German Naval Medical Institute, 24119 Kiel, Germany.
Cells. 2023 Oct 18;12(20):2479. doi: 10.3390/cells12202479.
The present study explores for the first time the effect of hyperbaric oxygen (HBO) on gingival mesenchymal stem cells' (G-MSCs) gene expression profile, intracellular pathway activation, pluripotency, and differentiation potential under an experimental inflammatory setup. G-MSCs were isolated from five healthy individuals ( = 5) and characterized. Single (24 h) or double (72 h) HBO stimulation (100% O2, 3 bar, 90 min) was performed under experimental inflammatory [IL-1β (1 ng/mL)/TNF-α (10 ng/mL)/IFN-γ (100 ng/mL)] and non-inflammatory micro-environment. Next Generation Sequencing and KEGG pathway enrichment analysis, G-MSCs' pluripotency gene expression, Wnt-/β-catenin pathway activation, proliferation, colony formation, and differentiation were investigated. G-MSCs demonstrated all mesenchymal stem/progenitor cells' characteristics. The beneficial effect of a single HBO stimulation was evident, with anti-inflammatory effects and induction of differentiation (, , ), proliferation/cell survival (, , , , ), migration () and osteogenic differentiation ( < 0.05). A second HBO stimulation at 72 h had a detrimental effect, significantly increasing the inflammation-induced cellular stress and ROS accumulation through , , and amplification and pathway enrichment ( < 0.05). Results outline a positive short-term single HBO anti-inflammatory, regenerative, and differentiation stimulatory effect on G-MSCs. A second (72 h) stimulation is detrimental to the same properties. The current results could open new perspectives in the clinical application of short-termed HBO induction in G-MSCs-mediated periodontal reparative/regenerative mechanisms.
本研究首次探索了高压氧 (HBO) 对牙龈间充质干细胞 (G-MSCs) 在实验性炎症环境下的基因表达谱、细胞内通路激活、多能性和分化潜能的影响。从五名健康个体 ( = 5) 中分离 G-MSCs 并进行鉴定。在实验性炎症 [IL-1β (1 ng/mL)/TNF-α (10 ng/mL)/IFN-γ (100 ng/mL)] 和非炎症微环境下,进行单次 (24 h) 或两次 (72 h) HBO 刺激 (100% O2,3 巴,90 分钟)。进行下一代测序和 KEGG 通路富集分析、G-MSCs 多能性基因表达、Wnt-/β-catenin 通路激活、增殖、集落形成和分化的研究。G-MSCs 表现出所有间充质干细胞/祖细胞的特征。单次 HBO 刺激的有益作用明显,具有抗炎作用和诱导分化 (,,),增殖/细胞存活 (,,,,),迁移 () 和成骨分化 ( < 0.05)。72 小时的第二次 HBO 刺激具有有害作用,通过 、 和 扩增以及通路富集显著增加炎症诱导的细胞应激和 ROS 积累 ( < 0.05)。结果概述了 HBO 对 G-MSCs 的短期单一抗炎、再生和分化刺激的积极作用。第二次 (72 h) 刺激对相同的特性是有害的。目前的结果可能为临床应用短期 HBO 诱导在 G-MSCs 介导的牙周修复/再生机制中开辟新的视角。