首页|Restoring sweat gland function in mice using regenerative sweat gland cells derived from chemically reprogrammed human epidermal keratinocytes

Restoring sweat gland function in mice using regenerative sweat gland cells derived from chemically reprogrammed human epidermal keratinocytes

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Restoring sweat gland function in mice using regenerative sweat gland cells derived from chemically reprogrammed human epidermal keratinocytes
The regeneration of sweat glands(SwGs)plays a pivotal role in the functional recovery of extensive skin wounds.Recent research has illuminated the possibility of reprogramming human epidermal ker-atinocytes(HEKs)into induced SwG cells through the ectopic expression of ectodysplasin A.However,the clinical application of this genetic manipulation approach is inherently limited.In this study,we pre-sent findings demonstrating that a combination of six compounds can effectively and speedily reprogram HEKs in culture into fully functional SwG cells.These chemically induced SwG-like cells(ciSGCs)closely resemble the morphology,phenotypes,and functional properties of human primary SwG ductal cells.Furthermore,ciSGCs can be stimulated to differentiate into mature SwG cell types in vitro.In a 3D culture system,they can also generate SwG organoids that exhibit structural and biological features akin to native SwGs.Upon transplantation into scalded mouse paw skin,ciSGCs significantly expedited cuta-neous wound healing and completely restored the structural and functional aspects of the SwGs.In con-clusion,the small molecule cocktail-directed SwG reprogramming offers a non-transgenic and controllable strategy for producing high-quality,clinical-grade SwG cells,showing immense potential for the treatment of burn patients.

Human epidermal keratinocytesSweat glandRegenerationChemical reprogramming

Jiangbing Xiang、Huating Chen、Hongliang Zhang、Lu Wu、Yan Li、Shuaifei Ji、Wei Pi、Shaoyuan Cui、Lei Dong、Xiaobing Fu、Xiaoyan Sun

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Research Center for Tissue Repair and Regeneration Affiliated to the Medical Innovation Research Department,PLA General Hospital and PLA Medical College,State Key Laboratory of Trauma and Chemical Poisoning,PLA Key Laboratory of Tissue Repair and Regenerative Medicine and Beijing Key Research Laboratory of Skin Injury,Repair and Regeneration,Research Unit of Trauma Care,Tissue Repair and Regeneration,Chinese Academy of Medical Sciences,2019RU051,Beijing 100048,China

State Key Laboratory of Pharmaceutical Bi

Institute of Basic Medical Sciences,Chine

Department of Nephrology,the First Medical Center of PLA General Hospital,State Key Laboratory of Kidney Diseases,Beijing 100730,China

State Key Laboratory of Pharmaceutical Biotechnology,School of Life Sciences,Nanjing University,Nanjing 210023,China

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Human epidermal keratinocytes Sweat gland Regeneration Chemical reprogramming

2024

10.1016/j.scib.2024.11.003

科学通报(英文版)
中国科学院

科学通报(英文版)

CSTPCD
ISSN：1001-6538
年,卷(期)：2024.69(24)