Jiang C M, Liu J, Zhao J Y, Xiao L, An S, Gou Y C, Quan H X, Cheng Q, Zhang Y L, He W, Wang Y T, Yu W J, Huang Y F, Yi Y T, Chen Y, Wang J
State Key Laboratory of Oral Diseases, Department of Orthodontics, West China Hospital of Stomatology, Sichuan University, Chendu, Sichuan, China.
Laboratory of Stem Cell Biology, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
J Dent Res. 2015 Jan;94(1):69-77. doi: 10.1177/0022034514557671. Epub 2014 Nov 17.
The environment of bone marrow mesenchymal stem cells (MSCs) is hypoxic, which plays an important role in maintaining their self-renewal potential and undifferentiated state. MSCs have been proven to possess immunomodulatory properties and have been used clinically to treat autoimmune diseases. Here, we tested the effects of hypoxia on the immunomodulatory properties of MSCs and examined its possible underlying mechanisms. We found that hypoxic stimulation promoted the immunomodulatory properties of human gingiva-derived mesenchymal stem cells (hGMSCs) by enhancing the suppressive effects of hGMSCs on peripheral blood mononuclear cells (PBMCs). The proliferation of PBMCs was significantly inhibited, while the apoptosis of PBMCs was increased, which was associated with the Fas ligand (FasL) expression of hGMSCs. The in vivo study showed that systemically infused hGMSCs could enhance skin wound repair, and 24-h hypoxic stimulation significantly promoted the reparative capacity of hGMSCs. For mechanism, hGMSC treatment inhibited the local inflammation of injured skin by suppressing the inflammatory cells, reducing the pro-inflammatory cytokine tumor necrosis factor-α (TNF-α), and increasing anti-inflammatory cytokine interleukin-10 (IL-10), which was promoted by hypoxia. Hypoxia preconditioning may be a good optimizing method to promote the potential of MSCs for the future cell-based therapy.
骨髓间充质干细胞（MSCs）所处的环境是低氧的，这在维持其自我更新潜能和未分化状态方面发挥着重要作用。MSCs已被证明具有免疫调节特性，并已在临床上用于治疗自身免疫性疾病。在此，我们测试了低氧对MSCs免疫调节特性的影响，并探究了其可能的潜在机制。我们发现，低氧刺激通过增强人牙龈来源的间充质干细胞（hGMSCs）对外周血单个核细胞（PBMCs）的抑制作用，促进了hGMSCs的免疫调节特性。PBMCs的增殖受到显著抑制，而PBMCs的凋亡增加，这与hGMSCs的Fas配体（FasL）表达有关。体内研究表明，全身输注hGMSCs可增强皮肤伤口修复能力，24小时的低氧刺激显著促进了hGMSCs的修复能力。就机制而言，hGMSC治疗通过抑制炎症细胞、降低促炎细胞因子肿瘤坏死因子-α（TNF-α）以及增加抗炎细胞因子白细胞介素-10（IL-10）来抑制受损皮肤的局部炎症，而低氧可促进这些作用。低氧预处理可能是一种促进MSCs潜能的良好优化方法，用于未来基于细胞的治疗。
