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    In vivo reprogramming of wound-resident cells generates skin epithelial tissue

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    Type
    Article
    Authors
    Kurita, Masakazu
    Araoka, Toshikazu
    Hishida, Tomoaki
    O’Keefe, David D.
    Takahashi, Yuta
    Sakamoto, Akihisa
    Sakurai, Masahiro
    Suzuki,Keiichiro
    Wu, Jun
    Yamamoto, Mako
    Hernandez-Benitez, Reyna
    Ocampo, Alejandro
    Reddy, Pradeep
    Shokhirev, Maxim Nikolaievich
    Magistretti, Pierre J. cc
    Núñez Delicado, Estrella
    Eto, Hitomi
    Harii, Kiyonori
    Izpisua Belmonte, Juan Carlos
    KAUST Department
    Biological and Environmental Sciences and Engineering (BESE) Division
    Bioscience Program
    Date
    2018-09-05
    Online Publication Date
    2018-09-05
    Print Publication Date
    2018-09
    Permanent link to this record
    http://hdl.handle.net/10754/630520
    
    Metadata
    Show full item record
    Abstract
    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.
    Citation
    Kurita M, Araoka T, Hishida T, O’Keefe DD, Takahashi Y, et al. (2018) In vivo reprogramming of wound-resident cells generates skin epithelial tissue. Nature 561: 243–247. Available: http://dx.doi.org/10.1038/s41586-018-0477-4.
    Sponsors
    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).
    Publisher
    Springer Nature
    Journal
    Nature
    DOI
    10.1038/s41586-018-0477-4
    Additional Links
    https://www.nature.com/articles/s41586-018-0477-4
    ae974a485f413a2113503eed53cd6c53
    10.1038/s41586-018-0477-4
    Scopus Count
    Collections
    Articles; Biological and Environmental Science and Engineering (BESE) Division; Bioscience Program

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