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Our previous studies have identified epidermal stem cells (ESCs) as critical for wound healing and HS remodelling, with its extracellular vesicles (EVs) playing a vital role. However, the specific mechanisms remain unclear. In this study, we first discovered that ESC\u2010EVs could effectively induce the mesenchymal\u2010epidermal transition (MET) of HS fibroblasts (HSFs) and inhibit their biological activity. Furthermore, by next\u2010generation sequencing and multiplexed CRISPR\/Cas9 system, we elucidated that this therapeutic effect is mediated by the miR\u2010200 family (miR\u2010200s) encapsulated in ESC\u2010EVs, which targeted and inhibited ZEB1 and ZEB2 in HSFs. This vital role and mechanism have been thoroughly validated in both in vitro cell experiments and in vivo rat tail HS (RHS) models. These findings not only shed light on a previously unidentified mechanism of ESC\u2010EVs for HS, but also provide potential novel targets and strategies for its precise treatment.<\/jats:p>","DOI":"10.1002\/jev2.70160","type":"journal-article","created":{"date-parts":[[2025,9,16]],"date-time":"2025-09-16T08:00:04Z","timestamp":1758009604000},"source":"Crossref","is-referenced-by-count":8,"title":["Epidermal Stem Cell\u2010Derived Extracellular Vesicles Induce Fibroblasts Mesenchymal\u2010Epidermal Transition to Alleviate Hypertrophic Scar Formation via miR\u2010200s Inhibition of ZEB1 and 2"],"prefix":"10.1002","volume":"14","author":[{"given":"Miao","family":"Zhen","sequence":"first","affiliation":[{"name":"Department of Burn and Wound Repair The First Affiliated Hospital of Sun Yat\u2010sen University  Guangzhou Guangdong Province China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juntao","family":"Xie","sequence":"additional","affiliation":[{"name":"Department 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