Department of Restorative Dental Sciences, College of Dentistry, King Saud University, Riyadh 11612, Saudi Arabia.
Therapeutics & Biomarker Discovery for Clinical Applications, Stem Cell & Tissue Re-Engineering Program, King Faisal Specialist Hospital and Research Centre, P.O. Box 3354, Riyadh 11211, Saudi Arabia.
Cells. 2022 Dec 28;12(1):122. doi: 10.3390/cells12010122.
An interconnection between tissue inflammation and regeneration has been established through the regulation of defense and repair mechanisms within diseased dental tissue triggered by the release of immune-resolvent mediators. To better our understanding of the role of specific pro-resolving mediators (SPMs) in inflamed human bone marrow-derived mesenchymal stem cells (hBMMSCs), we studied the effects of Resolvin E1 (RvE1) and Maresin 1 (MaR1) in lipopoly-saccharide (LPS) stimulated hBMMSCs. The hBMMSCs were divided into five different groups, each of which was treated with or without SPMs. Group-1: negative control (no LPS stimulation), Group-2: positive control (LPS-stimulated), Group-3: RvE1 100 nM + 1 μg/mL LPS, Group-4: MaR1 100 nM + 1 µg/mL LPS, and Group-5: RvE1 100 nM + MaR1100 nM + 1 μg/mL LPS. Cell proliferation, apoptosis, migration, colony formation, Western blotting, cytokine array, and LC/MS analysis were all performed on each group to determine the impact of SPMs on inflammatory stem cells. According to our data, RvE1 plus MaR1 effectively reduced inflammation in hBMMSCs. In particular, IL-4, 1L-10, and TGF-β1 activation and downregulation of RANKL, TNF-α, and IFN-γ compared to groups receiving single SPM were shown to be significantly different (Group 3 and 4). In addition, the LC/MS analysis revealed the differentially regulated peptide's role in immunological pathways that define the cellular state against inflammation. Inflamed hBMMSCs treated with a combination of Resolvin E1 (RvE1) and Maresin 1 (MaR1) promoted the highest inflammatory resolution compared to the other groups; this finding suggests a potential new approach of treating bacterially induced dental infections.
组织炎症与再生之间的联系已经通过受免疫溶解介质释放触发的病变牙组织内防御和修复机制的调节得以确立。为了更好地理解特定的促解决介质(SPM)在炎性人骨髓间充质干细胞(hBMMSCs)中的作用,我们研究了 RvE1 和 MaR1 在脂多糖(LPS)刺激的 hBMMSCs 中的作用。将 hBMMSCs 分为五组,每组均用或不用 SPM 处理。组 1:阴性对照(无 LPS 刺激),组 2:阳性对照(LPS 刺激),组 3:RvE1100nM+1μg/mL LPS,组 4:MaR1100nM+1μg/mL LPS,组 5:RvE1100nM+MaR1100nM+1μg/mL LPS。对每组细胞进行增殖、凋亡、迁移、集落形成、Western blot、细胞因子阵列和 LC/MS 分析,以确定 SPM 对炎性干细胞的影响。根据我们的数据,RvE1 和 MaR1 的联合使用可有效减轻 hBMMSCs 的炎症。特别是与单独接受 SPM 的组相比,IL-4、IL-10 和 TGF-β1 的激活以及 RANKL、TNF-α 和 IFN-γ 的下调显示出明显的差异(组 3 和 4)。此外,LC/MS 分析揭示了差异调节肽在免疫途径中的作用,这些途径定义了针对炎症的细胞状态。与其他组相比,用 RvE1 和 MaR1 处理的炎性 hBMMSCs 促进了最高的炎症缓解,这一发现为治疗细菌诱导的牙齿感染提供了一种新的潜在方法。