Skin graft with dermis and appendages generated in vivo by cell competition

Hisato Nagano, Naoaki Mizuno (), Hideyuki Sato, Eiji Mizutani, Ayaka Yanagida, Mayuko Kano, Mariko Kasai, Hiromi Yamamoto, Motoo Watanabe, Fabian Suchy, Hideki Masaki and Hiromitsu Nakauchi ()
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Hisato Nagano: University of Tokyo
Naoaki Mizuno: University of Tokyo
Hideyuki Sato: University of Tokyo
Eiji Mizutani: University of Tokyo
Ayaka Yanagida: University of Tokyo
Mayuko Kano: University of Tokyo
Mariko Kasai: University of Tokyo
Hiromi Yamamoto: University of Tokyo
Motoo Watanabe: University of Tokyo
Fabian Suchy: Stanford University School of Medicine
Hideki Masaki: University of Tokyo
Hiromitsu Nakauchi: University of Tokyo

Nature Communications, 2024, vol. 15, issue 1, 1-12

Abstract: Abstract Autologous skin grafting is a standard treatment for skin defects such as burns. No artificial skin substitutes are functionally equivalent to autologous skin grafts. The cultured epidermis lacks the dermis and does not engraft deep wounds. Although reconstituted skin, which consists of cultured epidermal cells on a synthetic dermal substitute, can engraft deep wounds, it requires the wound bed to be well-vascularized and lacks skin appendages. In this study, we successfully generate complete skin grafts with pluripotent stem cell-derived epidermis with appendages on p63 knockout embryos’ dermis. Donor pluripotent stem cell-derived keratinocytes encroach the embryos’ dermis by eliminating p63 knockout keratinocytes based on cell-extracellular matrix adhesion mediated cell competition. Although the chimeric skin contains allogenic dermis, it is engraftable as long as autologous grafts. Furthermore, we could generate semi-humanized skin segments by human keratinocytes injection into the amnionic cavity of p63 knockout mice embryos. Niche encroachment opens the possibility of human skin graft production in livestock animals.

Date: 2024
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DOI: 10.1038/s41467-024-47527-7

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