Dong Liang, Hao Haojie, Liu Jiejie, Ti Dongdong, Tong Chuan, Hou Qian, Li Meirong, Zheng Jingxi, Liu Gang, Fu Xiaobing, Han Weidong
Institute of Basic Medicine Science, College of Life Science, Chinese PLA General Hospital, Beijing 100853, China.
Stem Cells Int. 2017;2017:3738071. doi: 10.1155/2017/3738071. Epub 2017 Feb 27.
Mesenchymal stem cells (MSCs) can affect the microenvironment of a wound and thereby accelerate wound healing. Wnt proteins act as key mediators of skin development and participate in the formation of skin appendages such as hair. The mechanisms of action of MSCs and Wnt proteins on skin wounds are largely unknown. Here, we prepared a Wnt7a-containing conditioned medium (Wnt-CM) from the supernatant of cultured human umbilical cord-MSCs (UC-MSCs) overexpressing Wnt7a in order to examine the effects of this CM on cutaneous healing. Our results revealed that Wnt-CM can accelerate wound closure and induce regeneration of hair follicles. Meanwhile, Wnt-CM enhanced expression of extracellular matrix (ECM) components and cell migration of fibroblasts but inhibited the migratory ability and expression of K6 and K16 in keratinocytes by enhancing expression of c-Myc. However, we found that the CM of fibroblasts treated with Wnt-CM (HF-CM) can also promote wound repair and keratinocyte migration; but there was no increase in the number of hair follicles of regeneration. These data indicate that Wnt7a and UC-MSCs have synergistic effects: they can accelerate wound repair and induce hair regeneration via cellular communication in the wound microenvironment. Thus, this study opens up new avenues of research on the mechanisms underlying wound repair.
间充质干细胞（MSCs）可影响伤口的微环境，从而加速伤口愈合。Wnt蛋白是皮肤发育的关键介质，参与毛发等皮肤附属器的形成。MSCs和Wnt蛋白对皮肤伤口的作用机制尚不清楚。在此，我们从过表达Wnt7a的培养人脐带间充质干细胞（UC-MSCs）的上清液中制备了含Wnt7a的条件培养基（Wnt-CM），以研究该条件培养基对皮肤愈合的影响。我们的结果显示，Wnt-CM可加速伤口闭合并诱导毛囊再生。同时，Wnt-CM增强了细胞外基质（ECM）成分的表达和成纤维细胞的细胞迁移，但通过增强c-Myc的表达抑制了角质形成细胞的迁移能力以及K6和K16的表达。然而，我们发现用Wnt-CM处理的成纤维细胞的条件培养基（HF-CM）也可促进伤口修复和角质形成细胞迁移；但再生毛囊的数量没有增加。这些数据表明Wnt7a和UC-MSCs具有协同作用：它们可通过伤口微环境中的细胞通讯加速伤口修复并诱导毛发再生。因此，本研究为伤口修复潜在机制的研究开辟了新途径。
