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 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 Magistretti, Estrella Núñez Delicado, Hitomi Eto, Kiyonori Harii, Juan Carlos Izpisua Belmonte

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94 Scopus citations

Abstract

Large cutaneous ulcers are, in severe cases, life threatening^1,2. As the global population ages, non-healing ulcers are becoming increasingly common^1,2. 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)	243-270
Number of pages	28
Journal	Nature
Volume	561
Issue number	7722
DOIs	https://doi.org/10.1038/s41586-018-0477-4
State	Published - 2018
Externally published	Yes

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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., Delicado, E. N., Eto, H., Harii, K., & Belmonte, J. C. I. (2018). In vivo reprogramming of wound-resident cells generates skin epithelial tissue. Nature, 561(7722), 243-270. https://doi.org/10.1038/s41586-018-0477-4

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, P, Delicado, EN, Eto, H, Harii, K & Belmonte, JCI 2018, 'In vivo reprogramming of wound-resident cells generates skin epithelial tissue', Nature, vol. 561, no. 7722, pp. 243-270. https://doi.org/10.1038/s41586-018-0477-4

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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 Pierre Magistretti and Delicado, {Estrella N{\'u}{\~n}ez} and Hitomi Eto and Kiyonori Harii and Belmonte, {Juan Carlos Izpisua}",

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

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AU - Araoka, Toshikazu

AU - Hishida, Tomoaki

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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

PY - 2018

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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.

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

Abstract

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