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Development of de novo epithelialization method for treatment of cutaneous ulcers
Masakazu Kurita1, Juan Carlos Izpisua Belmonte2, Keiichiro Suzuki3
1Department 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.
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