Development of de novo epithelialization method for treatment of cutaneous ulcers

J Dermatol Sci. 2019 Jul;95(1):8-12. doi: 10.1016/j.jdermsci.2019.06.006. Epub 2019 Jun 22.


Cutaneous ulcers are a common cause of morbidity. We have developed a de novo epithelialization method for treating cutaneous ulcers by means of reprogramming wound-resident mesenchymal cells in vivo into cells able to form a stratified epithelium: induced stratified epithelial progenitors (iSEPs). Administration of 4 transcription factors (DNP63A, GRHL2, TFAP2A, and cMYC) expressed via adeno-associated viral vectors enabled generation of epithelial cells and tissues, thereby acheiving de novo epithelialization from the surfaces of cutaneous ulcers in a mouse model. Generated epithelia, having barrier functions equivalent to the original epidermis, were maintained for more than 6 months. Our findings constitute a proof of concept for future development towards innovative therapies for cutaneous ulcers via de novo epithelialization.

Keywords: Direct conversion; Direct reprogramming cutaneous ulcer; Epithelialization; Lineage reprogramming; Wound healing.

MeSH terms

  • Animals
  • Cell Differentiation / genetics
  • Dependovirus / genetics
  • Disease Models, Animal
  • Fibroblasts
  • Genetic Therapy / methods*
  • Genetic Vectors / administration & dosage
  • Genetic Vectors / genetics
  • Humans
  • Induced Pluripotent Stem Cells
  • Keratinocytes
  • Mesenchymal Stem Cells / physiology
  • Mice
  • Mice, Transgenic
  • Re-Epithelialization / genetics*
  • Skin / pathology
  • Skin Ulcer / pathology
  • Skin Ulcer / therapy*
  • Transcription Factors / genetics*


  • Transcription Factors