Effects of Hypoxia on the Immunomodulatory Properties of Human Gingiva–Derived Mesenchymal Stem Cells

间充质干细胞 外周血单个核细胞 细胞因子 缺氧(环境) 肿瘤坏死因子α 干细胞 炎症 免疫学 骨髓 癌症研究 伤口愈合 医学
作者
Chunmiao Jiang,Junyong Liu,J.Y. Zhao,L. Xiao,An S,Yongchao Gou,H.X. Quan,Q. Cheng,Yuting Zhang,Weijun He,Yan Wang,Wen-jing Yu,Yi-fan Huang,Y.T. Yi,Yangxi Chen,Jiongke Wang
出处
期刊:Journal of Dental Research [SAGE]
卷期号:94 (1): 69-77 被引量:52
标识
DOI:10.1177/0022034514557671
摘要

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.
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