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 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.
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