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

Masakazu Kurita; Toshikazu Araoka; Tomoaki Hishida; David D. O’Keefe; Yuta Takahashi; Akihisa Sakamoto; Masahiro Sakurai; Keiichiro Suzuki; Jun Wu; Mako Yamamoto; Reyna Hernandez-Benitez; Alejandro Ocampo; Pradeep Reddy; Maxim Nikolaievich Shokhirev; Pierre J. Magistretti; Estrella Núñez Delicado; Hitomi Eto; Kiyonori Harii; Juan Carlos Izpisua Belmonte

doi:10.1038/s41586-018-0477-4

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

Masakazu Kurita, Toshikazu Araoka, Tomoaki Hishida, David D. O’Keefe, Yuta Takahashi, Akihisa Sakamoto, Masahiro Sakurai, Keiichiro Suzuki, Jun Wu, Mako Yamamoto, Reyna Hernandez-Benitez, Alejandro Ocampo, Pradeep Reddy, Maxim Nikolaievich Shokhirev, Pierre J. Magistretti, Estrella Núñez Delicado, Hitomi Eto, Kiyonori Harii, Juan Carlos Izpisua Belmonte

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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.

Original language	English (US)
Pages (from-to)	243-247
Number of pages	5
Journal	Nature
Volume	561
Issue number	7722
DOIs	https://doi.org/10.1038/s41586-018-0477-4
State	Published - Sep 5 2018

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Kurita, M., Araoka, T., Hishida, T., O’Keefe, D. D., Takahashi, Y., Sakamoto, A., Sakurai, M., Suzuki, K., Wu, J., Yamamoto, M., Hernandez-Benitez, R., Ocampo, A., Reddy, P., Shokhirev, M. N., Magistretti, P. J., Núñez Delicado, E., Eto, H., Harii, K., & Izpisua Belmonte, J. C. (2018). In vivo reprogramming of wound-resident cells generates skin epithelial tissue. Nature, 561(7722), 243-247. https://doi.org/10.1038/s41586-018-0477-4

@article{b24ead9c4f564e2b987aef26cdae9119,

title = "In vivo reprogramming of wound-resident cells generates skin epithelial tissue",

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.",

author = "Masakazu Kurita and Toshikazu Araoka and Tomoaki Hishida and O{\textquoteright}Keefe, {David D.} and Yuta Takahashi and Akihisa Sakamoto and Masahiro Sakurai and Keiichiro Suzuki and Jun Wu and Mako Yamamoto and Reyna Hernandez-Benitez and Alejandro Ocampo and Pradeep Reddy and Shokhirev, {Maxim Nikolaievich} and Magistretti, {Pierre J.} and {N{\'u}{\~n}ez Delicado}, Estrella and Hitomi Eto and Kiyonori Harii and {Izpisua Belmonte}, {Juan Carlos}",

note = "KAUST Repository Item: Exported on 2020-10-01 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 Cat{\'o}lica San Antonio de Murcia (UCAM).",

year = "2018",

month = sep,

day = "5",

doi = "10.1038/s41586-018-0477-4",

language = "English (US)",

volume = "561",

pages = "243--247",

journal = "Nature",

issn = "0028-0836",

publisher = "Nature Publishing Group",

number = "7722",

}

Kurita, M, Araoka, T, Hishida, T, O’Keefe, DD, Takahashi, Y, Sakamoto, A, Sakurai, M, Suzuki, K, Wu, J, Yamamoto, M, Hernandez-Benitez, R, Ocampo, A, Reddy, P, Shokhirev, MN, Magistretti, PJ, Núñez Delicado, E, Eto, H, Harii, K & Izpisua Belmonte, JC 2018, 'In vivo reprogramming of wound-resident cells generates skin epithelial tissue', Nature, vol. 561, no. 7722, pp. 243-247. https://doi.org/10.1038/s41586-018-0477-4

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 J.

AU - Núñez Delicado, Estrella

AU - Eto, Hitomi

AU - Harii, Kiyonori

AU - Izpisua Belmonte, Juan Carlos

N1 - KAUST Repository Item: Exported on 2020-10-01 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).

PY - 2018/9/5

Y1 - 2018/9/5

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://hdl.handle.net/10754/630520

UR - https://www.nature.com/articles/s41586-018-0477-4

UR - http://www.scopus.com/inward/record.url?scp=85054886413&partnerID=8YFLogxK

U2 - 10.1038/s41586-018-0477-4

DO - 10.1038/s41586-018-0477-4

M3 - Article

C2 - 30185909

SN - 0028-0836

VL - 561

SP - 243

EP - 247

JO - Nature

JF - Nature

IS - 7722

ER -

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

Abstract

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