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 and Juan Carlos Izpisua Belmonte ()
Additional contact information
Masakazu Kurita: The Salk Institute for Biological Studies
Toshikazu Araoka: The Salk Institute for Biological Studies
Tomoaki Hishida: The Salk Institute for Biological Studies
David D. O’Keefe: The Salk Institute for Biological Studies
Yuta Takahashi: The Salk Institute for Biological Studies
Akihisa Sakamoto: The Salk Institute for Biological Studies
Masahiro Sakurai: The Salk Institute for Biological Studies
Keiichiro Suzuki: The Salk Institute for Biological Studies
Jun Wu: The Salk Institute for Biological Studies
Mako Yamamoto: The Salk Institute for Biological Studies
Reyna Hernandez-Benitez: The Salk Institute for Biological Studies
Alejandro Ocampo: The Salk Institute for Biological Studies
Pradeep Reddy: The Salk Institute for Biological Studies
Maxim Nikolaievich Shokhirev: The Salk Institute for Biological Studies
Pierre Magistretti: King Abdullah University of Science & Technology (KAUST)
Estrella Núñez Delicado: Campus de los Jerónimos
Hitomi Eto: Kyorin University School of Medicine
Kiyonori Harii: Kyorin University School of Medicine
Juan Carlos Izpisua Belmonte: The Salk Institute for Biological Studies

Nature, 2018, vol. 561, issue 7722, 243-247

Abstract: 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.

Keywords: Adeno-associated Viruses (AAV); Adipose-derived Stromal Cells; Primary Keratinocytes; Surrounding Skin; Transepidermal Water Loss (TEWL) (search for similar items in EconPapers)
Date: 2018
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Citations: View citations in EconPapers (2)

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DOI: 10.1038/s41586-018-0477-4

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