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

Development of de novo epithelialization method for treatment of cutaneous ulcers.

Author information

1
Department of Plastic and Aesthetic Surgery, The University of Tokyo Hospital, Japan. Electronic address: kuritam-pla@h.u-tokyo.ac.jp.
2
Gene expression Laboratory, Salk Institute for Biological Studies, United States.
3
Institute for Advanced Co-Creation Studies, Osaka University, Japan; Graduate School of Engineering Science, Osaka University, Japan.
4
Department of Plastic and Aesthetic Surgery, The University of Tokyo Hospital, Japan.

Abstract

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

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