TY - JOUR
T1 - In vivo reprogramming of wound-resident cells generates skin epithelial tissue
AU - Kurita, Masakazu
AU - Araoka, Toshikazu
AU - Hishida, Tomoaki
AU - O’keefe, David D.
AU - Takahashi, Yuta
AU - Sakamoto, Akihisa
AU - Sakurai, Masahiro
AU - Suzuki, Keiichiro
AU - Wu, Jun
AU - Yamamoto, Mako
AU - Hernandez-Benitez, Reyna
AU - Ocampo, Alejandro
AU - Reddy, Pradeep
AU - Shokhirev, Maxim Nikolaievich
AU - Magistretti, Pierre
AU - Delicado, Estrella Núñez
AU - Eto, Hitomi
AU - Harii, Kiyonori
AU - Belmonte, Juan Carlos Izpisua
N1 - Funding Information:
Acknowledgements 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).
Funding Information:
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 Copyright:
© 2018 Springer Nature Limited. All rights reserved.
PY - 2018
Y1 - 2018
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85054886413&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85054886413&partnerID=8YFLogxK
U2 - 10.1038/s41586-018-0477-4
DO - 10.1038/s41586-018-0477-4
M3 - Article
C2 - 30185909
AN - SCOPUS:85054886413
SN - 0028-0836
VL - 561
SP - 243
EP - 270
JO - Nature
JF - Nature
IS - 7722
ER -