缺氧通过促进IL-10分泌增强胎盘间充质干细胞抑制烫伤皮肤瘢痕形成的作用研究

The repair of deep skin burn can cause scarring. Fibroblasts, macrophages and endothelial cells are important effector cells of burn repair, and the role of cytokines are bi-directional. Placenta-derived mesenchymal stem cells (pMSCs) have good prospects in burns treatment. We found that pMSCs hypoxic culture medium significantly inhibit the scarring of burn skin, and found increased IL-10 in pMSCs hypoxic culture medium may affect the proliferation，migration and collagen synthesis of fibroblasts in inflammatory environment. Therefore, it is speculated that " Hypoxia enhances the inhibition effect of placental mesenchymal stem cells on scalded skin scarring by promoting the secretion of IL-10." To confirm this hypothesis, we established mouse model of skin burns and fibroblast ,macrophages and endothelial cells model in inflammatory environment.From the levels of animals and cells , we observe the effect of IL-10 secreted by pMSCs on burn skin scarring and clarify their mechanism, and reveal signaling pathway of IL-10 secretion from pMSCs stimulated by hypoxia. This study provides a new perspective for pMSCs to be applicated in burn repair , and also provides a new way of thinking for the suppression of skin burns scarring.

皮肤深度烫伤修复时有瘢痕形成。成纤维细胞、巨噬细胞及血管内皮细胞是修复的效应细胞，细胞因子的作用具有双向性。胎盘间充质干细胞(placenta-derived mesenchymal stem cells，pMSCs)在烫伤治疗中有很好的应用前景。我们前期发现pMSCs缺氧培养液明显抑制烫伤皮肤瘢痕形成，pMSCs缺氧培养液中增多的IL-10可抑制炎症环境中成纤维细胞增殖、迁移及胶原合成。因此推测“缺氧通过促进IL-10分泌增强pMSCs对烫伤皮肤瘢痕形成的抑制作用”。为证实该假说，我们建立小鼠皮肤烫伤模型及炎症环境中的成纤维细胞、巨噬细胞及血管内皮细胞模型，在动物及细胞两个水平观察pMSCs缺氧培养液中IL-10对烫伤皮肤瘢痕形成的抑制作用并阐明其机制，同时揭示缺氧刺激pMSCs分泌IL-10的信号通路。本研究为pMSCs在烫伤修复中的应用提供了新视角, 为抑制烫伤皮肤瘢痕形成提供新思路