Thyroxine (T4) may promote re-epithelialisation and angiogenesis in wounded human skin ex vivo

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Energy Metabolism / drug effects
  • Epidermis / metabolism*
  • Epidermis / pathology
  • Female
  • Fibroblasts / metabolism
  • Fibroblasts / pathology
  • Gene Expression Regulation / drug effects
  • Humans
  • Keratins / biosynthesis
  • Male
  • Middle Aged
  • Neovascularization, Physiologic / drug effects*
  • Re-Epithelialization / drug effects*
  • Thyroxine / pharmacology*
  • Tissue Culture Techniques


  • Keratins
  • Thyroxine

Grants and funding

This work was supported in part by a grant from the Federal Ministry of Economics, Germany (AiF/ZIM Programme) to R.P. G-Y Zhang was supported by 2011 Chinese government award for outstanding self-financed students abroad (China Scholarship Council) and National Natural Science Foundation of China (81101430).