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

被引:7
作者
Nagano, Hisato [1 ,2 ,3 ]
Mizuno, Naoaki [1 ,2 ,4 ]
Sato, Hideyuki [1 ,2 ]
Mizutani, Eiji [1 ,2 ,5 ]
Yanagida, Ayaka [1 ,2 ,6 ]
Kano, Mayuko [1 ,2 ,7 ]
Kasai, Mariko [1 ,2 ]
Yamamoto, Hiromi [1 ,2 ]
Watanabe, Motoo [1 ,2 ]
Suchy, Fabian [8 ]
Masaki, Hideki [1 ,2 ]
Nakauchi, Hiromitsu [1 ,2 ,8 ]
机构
[1] Univ Tokyo, Inst Med Sci, Ctr Stem Cell Biol & Regenerat Med, Div Stem Cell Therapy, 4-6-1 Shirokanedai,Minato Ku, Tokyo 1088639, Japan
[2] Tokyo Med & Dent Univ, Adv Res Inst, Stem Cell Therapy Lab, 1-5-45 Yushima,Bunkyo Ku, Tokyo 1138510, Japan
[3] Natl Def Med Coll, Dept Plast & Reconstruct Surg, 3-2 Namiki, Saitama 3598513, Japan
[4] Tokyo Med & Dent Univ, Ctr Expt Anim, Dept Expt Anim Model Human Dis, 1-5-45 Yushima,Bunkyo Ku, Tokyo 1138510, Japan
[5] Univ Tsukuba, Inst Med, Lab Stem Cell Therapy, 1-1-1 Tennodai, Tsukuba, Ibaraki 3058577, Japan
[6] Univ Tokyo, Dept Vet Anat, Yayoi 1-1-1,Bunkyo Ku, Tokyo 1138657, Japan
[7] St Marianna Univ, Dept Med, Metab & Endocrinol, Sch Med, 2-16-1 Sugao,Miyamae Ku, Kawasaki, Kanagawa 2168511, Japan
[8] Stanford Univ, Inst Stem Cell Biol & Regenerat Med, Sch Med, Stanford, CA 94305 USA
基金
日本学术振兴会;
关键词
STEM-CELLS; P63; INJECTION; PANCREAS; MOUSE; LIMB;
D O I
10.1038/s41467-024-47527-7
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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. Skin substitutes generated by tissue engineering have limited properties. Here, authors established niche encroachment method. Cell competition enabled skin organogenesis from allogeneic and xenogeneic stem cells on p63 knockout embryos, resulting in a complete skin graft on dermis with hair.
引用
收藏
页数:12
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