Department of Plastic and Reconstructive Surgery, Shanghai Ninth People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
Department of Dermatology, University of Lübeck, Lübeck, Germany.
PLoS One. 2019 Mar 29;14(3):e0212659. doi: 10.1371/journal.pone.0212659. eCollection 2019.
There is a pressing need for improved preclinical model systems in which to study human skin wound healing. Here, we report the development and application of a serum-free full thickness human skin wound healing model. Not only can re-epithelialization (epidermal repair) and angiogenesis be studied in this simple and instructive model, but the model can also be used to identify clinically relevant wound-healing promoting agents, and to dissect underlying candidate mechanisms of action in the target tissue. We present preliminary ex vivo data to suggest that Thyroxine (T4), which reportedly promotes skin wound healing in rodents in vivo, may promote key features of human skin wound healing. Namely, T4 stimulates re-epithelialisation and angiogenesis, and modulates both wound healing-associated epidermal keratin expression and energy metabolism in experimentally wound human skin. Functionally, the wound healing-promoting effects of T4 are at least partially mediated via fibroblast growth factor/fibroblast growth factor receptor-mediated signalling, since they could be significantly antagonized by bFGF-neutralizing antibody. Thus, this pragmatic, easy-to-use full-thickness human skin wound healing model provides a useful preclinical research tool in the search for clinically relevant candidate wound healing-promoting agents. These ex vivo data encourage further pre-clinical testing of topical T4 as a cost-efficient, novel agent in the management of chronic human skin wounds.
目前迫切需要改进临床前模型系统，以便研究人类皮肤伤口愈合。在这里，我们报告了一种无血清全层人类皮肤伤口愈合模型的开发和应用。在这个简单而有启发性的模型中，不仅可以研究再上皮化（表皮修复）和血管生成，还可以用于鉴定临床上相关的促进伤口愈合的药物，并剖析目标组织中潜在的作用机制。我们提出初步的离体数据表明，甲状腺素（T4）在体内促进啮齿动物皮肤伤口愈合，可能促进人类皮肤伤口愈合的关键特征。即 T4 刺激再上皮化和血管生成，并调节实验性伤口人类皮肤中与伤口愈合相关的表皮角蛋白表达和能量代谢。功能上，T4 的促伤口愈合作用至少部分通过成纤维细胞生长因子/成纤维细胞生长因子受体介导的信号转导介导，因为 bFGF 中和抗体可显著拮抗其作用。因此，这种实用、易于使用的全层人类皮肤伤口愈合模型为寻找临床上相关的候选促伤口愈合药物提供了有用的临床前研究工具。这些离体数据鼓励进一步对局部 T4 进行临床前测试，作为管理慢性人类皮肤伤口的一种具有成本效益的新型药物。
