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Current conventional medicines exhibit several drawbacks, including limited therapeutic effects, prolonged treatment periods, and high costs. As a novel cell\u2010free therapy, the umbilical cord\u2010derived mesenchymal stem cell (UCMSC) secretome may offer a promising approach for skin regeneration and rejuvenation. The UCMSC secretome is a collection of all proteins secreted by mesenchymal stem cells, including conditioned media, exosomes, and other substances. The UCMSC secretome has numerous abilities to accelerate acute wound healing, including high fibroblast and keratinocyte proliferative activity, pro\u2010angiogenesis, anti\u2010inflammation, anti\u2010fibrosis, and anti\u2010oxidative stress. Its impact on the four stages of wound healing is manifested by inducing the haemostasis phase, inhibiting the inflammation phase, promoting the proliferation phase, and regulating the remodelling phase. Furthermore, it is highly effective in the treatment of chronic wounds, alopecia, aging, and skin homeostasis disturbance. This review focuses on the clinical therapies and application prospects of the UCMSC secretome, encompassing its source, culture, separation, identification, storage, and pretreatment. Additionally, a discussion on the dosage, administration route, efficacy, and biosafety in the clinical situation is presented. This review aims to provide scientific support for the mechanistic investigation and clinical utilisation of the UCMSC secretome in wound healing and skin rejuvenation.<\/jats:p>","DOI":"10.1111\/cpr.13586","type":"journal-article","created":{"date-parts":[[2023,12,27]],"date-time":"2023-12-27T01:10:48Z","timestamp":1703639448000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":71,"title":["Umbilical cord\u2010derived mesenchymal stem cell secretome promotes skin regeneration and rejuvenation: From mechanism to therapeutics"],"prefix":"10.1111","volume":"57","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-7661-633X","authenticated-orcid":false,"given":"Xixian","family":"Li","sequence":"first","affiliation":[{"name":"Department of Plastic Surgery The Second Hospital of Dalian Medical University  Dalian Liaoning China"},{"name":"CAS Key Laboratory of Separation Science for Analytical Chemistry Dalian Institute of Chemical 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