Large cutaneous ulcers are, in severe cases, life threatening1,2. As the global population ages, non-healing ulcers are becoming increasingly common1,2. Treatment currently requires the transplantation of pre-existing epithelial components, such as skin grafts, or therapy using cultured cells2. Here we develop alternative supplies of epidermal coverage for the treatment of these kinds of wounds. We generated expandable epithelial tissues using in vivo reprogramming of wound-resident mesenchymal cells. Transduction of four transcription factors that specify the skin-cell lineage enabled efficient and rapid de novo epithelialization from the surface of cutaneous ulcers in mice. Our findings may provide a new therapeutic avenue for treating skin wounds and could be extended to other disease situations in which tissue homeostasis and repair are impaired.
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Data from the microarray, RNA-seq and miRNA microarray analyses have been deposited in the Gene Expression Omnibus (GEO) and ArrayExpress under accession numbers GSE85803, GSE106419 and E-MTAB-5055, respectively. All other relevant data that support the findings of this study are available from the corresponding author upon reasonable request.
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This work was supported by MEXT KAKENHI Grant numbers JP26293381(Grant-in-Aid for Scientific Research (B) to M.K.), JP23689073 (Grant-in-Aid for Young Scientists (A) to M.K.), JP21689046 (Grant-in-Aid for Young Scientists (A) to M.K.), Kyorin University research promotion award to M.K. (2013), JSPS Overseas Research Fellowships (2015–17) to M.K., and the Uehara Memorial Foundation Research Fellowship for Research Abroad (2017–18) to M.K. M.K. thanks H. Green for support materials. T.H. thanks F. Sugiyama for support materials. M.N.S. is supported by NIH-NCI CCSG: P30 014195 and The Leona M. and Harry B. Helmsley Charitable Trust. Work in the laboratory of J.C.I.B. was supported by the G. Harold and Leila Y. Mathers Charitable Foundation, The Leona M. and Harry B. Helmsley Charitable Trust, The Moxie Foundation, The Evergreen Foundation, Fundacion Dr. Pedro Guillen and Universidad Católica San Antonio de Murcia (UCAM).
Nature thanks S. Akita, V. Horsley, A. Lombardo and the other anonymous reviewer(s) for their contribution to the peer review of this work.