Skin organoid transplantation promotes tissue repair with scarless in frostbite.

Wenwen WANG; Pu LIU; Wendi ZHU; Tianwei LI; Ying WANG; Yujie WANG; Jun LI; Jie MA; Ling LENG

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Skin organoid transplantation promotes tissue repair with scarless in frostbite.

Author: Wenwen WANG ¹ ; Pu LIU ² ; Wendi ZHU ¹ ; Tianwei LI ² ; Ying WANG ¹ ; Yujie WANG ¹ ; Jun LI ¹ ; Jie MA ² ; Ling LENG ¹
Author Information

1. Stem Cell and Regenerative Medicine Lab, Institute of Clinical Medicine, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China.
2. State Key Laboratory of Medical Proteomics, Beijing Proteome Research Center, National Center for Protein Sciences (Beijing), Beijing Institute of Lifeomics, Beijing 102206, China.
Publication Type:Journal Article
Keywords: frostbite treatment; human-induced pluripotent stem cell; single-cell transcriptomics; skin frostbite; skin organoids
MeSH: Animals; Organoids/metabolism*; Mice; Humans; Wound Healing; Frostbite/metabolism*; Skin/pathology*; Induced Pluripotent Stem Cells/cytology*; Cicatrix/pathology*; Fibroblasts/metabolism*; Disease Models, Animal; Mice, Inbred C57BL; Extracellular Matrix/metabolism*; Male
From: Protein & Cell 2025;16(4):240-259
CountryChina
Language:English
Abstract: Frostbite is the most common cold injury and is caused by both immediate cold-induced cell death and the gradual development of localized inflammation and tissue ischemia. Delayed healing of frostbite often leads to scar formation, which not only causes psychological distress but also tends to result in the development of secondary malignant tumors. Therefore, a rapid healing method for frostbite wounds is urgently needed. Herein, we used a mouse skin model of frostbite injury to evaluate the recovery process after frostbite. Moreover, single-cell transcriptomics was used to determine the patterns of changes in monocytes, macrophages, epidermal cells, and fibroblasts during frostbite. Most importantly, human-induced pluripotent stem cell (hiPSC)-derived skin organoids combined with gelatin-hydrogel were constructed for the treatment of frostbite. The results showed that skin organoid treatment significantly accelerated wound healing by reducing early inflammation after frostbite and increasing the proportions of epidermal stem cells. Moreover, in the later stage of wound healing, skin organoids reduced the overall proportions of fibroblasts, significantly reduced fibroblast-to-myofibroblast transition by regulating the integrin α5β1-FAK pathway, and remodeled the extracellular matrix (ECM) through degradation and reassembly mechanisms, facilitating the restoration of physiological ECM and reducing the abundance of ECM associated with abnormal scar formation. These results highlight the potential application of organoids for promoting the reversal of frostbite-related injury and the recovery of skin functions. This study provides a new therapeutic alternative for patients suffering from disfigurement and skin dysfunction caused by frostbite.