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  3. 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

  • Sci Bull (Beijing). 2024 Dec 30;69(24):3908-3924. doi: 10.1016/j.scib.2024.11.003.
Jiangbing Xiang 1,  Huating Chen 2,  Hongliang Zhang 3,  Lu Wu 3,  Yan Li 3,  Shuaifei Ji 3,  Wei Pi 4,  Shaoyuan Cui 5,  Lei Dong 6,  Xiaobing Fu 7,  Xiaoyan Sun 8
Affiliations

Affiliations

  • 1 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 Biotechnology, School of Life Sciences, Nanjing University, Nanjing 210023, China.
  • 2 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; Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences School of Basic Medicine Peking Union Medical College, Beijing 100730, China; State Key Laboratory of Trauma, Burn and Combined Injury, Third Military Medical University, Chongqing 400038, China.
  • 3 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.
  • 4 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; Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences School of Basic Medicine Peking Union Medical College, Beijing 100730, China.
  • 5 Department of Nephrology, the First Medical Center of PLA General Hospital, State Key Laboratory of Kidney Diseases, Beijing 100730, China.
  • 6 State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing 210023, China. Electronic address: [email protected].
  • 7 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. Electronic address: [email protected].
  • 8 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. Electronic address: [email protected].
PMID: 39550273 DOI: 10.1016/j.scib.2024.11.003
Abstract

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 keratinocytes (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 present 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 cutaneous wound healing and completely restored the structural and functional aspects of the SwGs. In conclusion, 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.

Keywords

Chemical reprogramming; Human epidermal keratinocytes; Regeneration; Sweat gland.

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