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      Umbilical cord‐derived mesenchymal stem cell secretome promotes skin regeneration and rejuvenation: From mechanism to therapeutics

      review-article
      1 , 2 , 1 , 2 , 3 , , 1 ,
      Cell Proliferation
      John Wiley and Sons Inc.

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          Abstract

          How to effectively repair cutaneous wounds and promote skin rejuvenation has always been a challenging issue for clinical medicine and medical aesthetics. Current conventional medicines exhibit several drawbacks, including limited therapeutic effects, prolonged treatment periods, and high costs. As a novel cell‐free therapy, the umbilical cord‐derived 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‐angiogenesis, anti‐inflammation, anti‐fibrosis, and anti‐oxidative 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.

          Abstract

          This review can be separated into two sections, one on mechanisms and the other on applications. Acute and chronic wound healing, anti‐aging, hair follicle regeneration, and other skincare effects are all supported by the UCMSC secretome in a variety of ways. Different functions in four stages are skin regeneration mechanisms. The review also covers everything from secretome culture, separation, and pretreatment through dosage, administration route, efficacy, and biosafety in the clinic.

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          Most cited references132

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          Overview of Extracellular Vesicles, Their Origin, Composition, Purpose, and Methods for Exosome Isolation and Analysis

          The use of extracellular vesicles, specifically exosomes, as carriers of biomarkers in extracellular spaces has been well demonstrated. Despite their promising potential, the use of exosomes in the clinical setting is restricted due to the lack of standardization in exosome isolation and analysis methods. The purpose of this review is to not only introduce the different types of extracellular vesicles but also to summarize their differences and similarities, and discuss different methods of exosome isolation and analysis currently used. A thorough understanding of the isolation and analysis methods currently being used could lead to some standardization in the field of exosomal research, allowing the use of exosomes in the clinical setting to become a reality.
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            Wound repair and regeneration: mechanisms, signaling, and translation.

            The cellular and molecular mechanisms underpinning tissue repair and its failure to heal are still poorly understood, and current therapies are limited. Poor wound healing after trauma, surgery, acute illness, or chronic disease conditions affects millions of people worldwide each year and is the consequence of poorly regulated elements of the healthy tissue repair response, including inflammation, angiogenesis, matrix deposition, and cell recruitment. Failure of one or several of these cellular processes is generally linked to an underlying clinical condition, such as vascular disease, diabetes, or aging, which are all frequently associated with healing pathologies. The search for clinical strategies that might improve the body's natural repair mechanisms will need to be based on a thorough understanding of the basic biology of repair and regeneration. In this review, we highlight emerging concepts in tissue regeneration and repair, and provide some perspectives on how to translate current knowledge into viable clinical approaches for treating patients with wound-healing pathologies.
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              Wound Healing: A Cellular Perspective

              Wound healing is one of the most complex processes in the human body. It involves the spatial and temporal synchronization of a variety of cell types with distinct roles in the phases of hemostasis, inflammation, growth, re-epithelialization, and remodeling. With the evolution of single cell technologies, it has been possible to uncover phenotypic and functional heterogeneity within several of these cell types. There have also been discoveries of rare, stem cell subsets within the skin, which are unipotent in the uninjured state, but become multipotent following skin injury. Unraveling the roles of each of these cell types and their interactions with each other is important in understanding the mechanisms of normal wound closure. Changes in the microenvironment including alterations in mechanical forces, oxygen levels, chemokines, extracellular matrix and growth factor synthesis directly impact cellular recruitment and activation, leading to impaired states of wound healing. Single cell technologies can be used to decipher these cellular alterations in diseased states such as in chronic wounds and hypertrophic scarring so that effective therapeutic solutions for healing wounds can be developed.
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                Author and article information

                Contributors
                wangliang-dy@dmu.edu.cn
                zhaomuxin@126.com
                Journal
                Cell Prolif
                Cell Prolif
                10.1111/(ISSN)1365-2184
                CPR
                Cell Proliferation
                John Wiley and Sons Inc. (Hoboken )
                0960-7722
                1365-2184
                26 December 2023
                April 2024
                : 57
                : 4 ( doiID: 10.1111/cpr.v57.4 )
                : e13586
                Affiliations
                [ 1 ] Department of Plastic Surgery The Second Hospital of Dalian Medical University Dalian Liaoning China
                [ 2 ] CAS Key Laboratory of Separation Science for Analytical Chemistry Dalian Institute of Chemical Physics, Chinese Academy of Sciences Dalian Liaoning China
                [ 3 ] Research and Teaching Department of Comparative Medicine Dalian Medical University Dalian Liaoning China
                Author notes
                [*] [* ] Correspondence

                Liang Wang, Research and Teaching Department of Comparative Medicine, Dalian Medical University, No. 9, West Section of Lushun South Road, Dalian, Liaoning 116044, China.

                Email: wangliang-dy@ 123456dmu.edu.cn

                Muxin Zhao, Department of Plastic Surgery, The Second Hospital of Dalian Medical University, No.467, Zhongshan Road, Dalian, Liaoning 116023, China.

                Email: zhaomuxin@ 123456126.com

                Author information
                https://orcid.org/0009-0006-7661-633X
                https://orcid.org/0000-0003-4812-8276
                Article
                CPR13586
                10.1111/cpr.13586
                10984109
                38148579
                7debf841-4413-4925-b5ee-403ade95a168
                © 2023 The Authors. Cell Proliferation published by Beijing Institute for Stem Cell and Regenerative Medicine and John Wiley & Sons Ltd.

                This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

                History
                : 31 October 2023
                : 15 August 2023
                : 22 November 2023
                Page count
                Figures: 6, Tables: 1, Pages: 16, Words: 13695
                Funding
                Funded by: Dalian Medical University , doi 10.13039/501100012465;
                Award ID: DMU‐2&DICP UN202311
                Categories
                Review
                Reviews
                Custom metadata
                2.0
                April 2024
                Converter:WILEY_ML3GV2_TO_JATSPMC version:6.4.0 mode:remove_FC converted:01.04.2024

                Cell biology
                Cell biology

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