Shi Hui, Xu Xiao, Zhang Bin, Xu Jiahao, Pan Zhaoji, Gong Aihua, Zhang Xu, Li Rong, Sun Yaoxiang, Yan Yongmin, Mao Fei, Qian Hui, Xu Wenrong
Jiangsu Key Laboratory of Medical Science and Laboratory Medicine, School of Medicine, Jiangsu University, Zhenjiang, Jiangsu 212013, China.
Theranostics. 2017 Apr 10;7(6):1674-1688. doi: 10.7150/thno.18082. eCollection 2017.
Human umbilical cord-derived mesenchymal stem cells (hucMSCs) are suggested as a promising therapeutic tool in regenerative medicine, however, their efficacy requires improvement. Small molecules and drugs come up to be a convenient strategy in regulating stem cells fate and function. Here, we evaluated 3,3'-diindolylmethane (DIM), a natural small-molecule compound involved in the repairing effects of hucMSCs on a deep second-degree burn injury rat model. HucMSCs primed with 50 μM of DIM exhibited desirable repairing effects compared with untreated hucMSCs. DIM enhanced the stemness of hucMSCs, which was related to the activation of Wnt/β-catenin signaling. β-catenin inhibition impaired the healing effects of DIM-primed hucMSCs (DIM-hucMSCs) . Moreover, we demonstrated that DIM upregulated Wnt11 expression in hucMSC-derived exosomes. Wnt11 knockdown inhibited β-catenin activation and stemness induction in DIM-hucMSCs and abrogated their therapeutic effects . Thus, our findings indicate that DIM promotes the stemness of hucMSCs through increased exosomal Wnt11 autocrine signaling, which provides a novel strategy for improving the therapeutic effects of hucMSCs on wound healing.
人脐带间充质干细胞（hucMSCs）被认为是再生医学中一种有前景的治疗工具，然而，其疗效仍需提高。小分子和药物成为调控干细胞命运和功能的一种便捷策略。在此，我们评估了3,3'-二吲哚甲烷（DIM），这是一种天然小分子化合物，参与hucMSCs对深二度烧伤大鼠模型的修复作用。与未处理的hucMSCs相比，用50 μM DIM预处理的hucMSCs表现出理想的修复效果。DIM增强了hucMSCs的干性，这与Wnt/β-连环蛋白信号通路的激活有关。β-连环蛋白抑制削弱了DIM预处理的hucMSCs（DIM-hucMSCs）的愈合效果。此外，我们证明DIM上调了hucMSC来源外泌体中Wnt11的表达。Wnt11基因敲低抑制了DIM-hucMSCs中β-连环蛋白的激活和干性诱导，并消除了它们的治疗效果。因此，我们的研究结果表明，DIM通过增加外泌体Wnt11自分泌信号促进hucMSCs的干性，这为提高hucMSCs对伤口愈合的治疗效果提供了一种新策略。
