Minjie Liu, Ganqin Ye, Ruiyang Li, Tenghui Gao, Caiwei Zhuang, Shiyun Huang, Sheng Wang, Jinhua Hu, Andy Peng Xiang, Mei Hua Jiang
{"title":"成纤维细胞来源的细胞外囊泡改善皮肤损伤微环境，促进伤口愈合。","authors":"Minjie Liu, Ganqin Ye, Ruiyang Li, Tenghui Gao, Caiwei Zhuang, Shiyun Huang, Sheng Wang, Jinhua Hu, Andy Peng Xiang, Mei Hua Jiang","doi":"10.1002/cbin.70063","DOIUrl":null,"url":null,"abstract":"<p><p>Fibroblasts are pivotal cellular components in cutaneous wound healing and are regarded as promising therapeutic candidates. However, their functional heterogeneity within tissue microenvironments significantly limits their clinical application. In contrast, whether fibroblast-derived extracellular vesicles (EVs) can overcome fibroblast heterogeneity while retaining the bioactivity and regenerative potential of homeostatic fibroblasts remains unclear. In this study, we systematically analyzed and compared the therapeutic potential and functional advantages of human dermal fibroblast-derived EVs (hDF-EVs) in promoting cutaneous wound healing. Our findings highlight the translational potential of fibroblast-derived EVs as a novel strategy to improve clinical outcomes for skin injuries. hDF-EVs were internalized by fibroblasts and keratinocytes at the wound margins, thereby attenuating early inflammatory responses and accelerating tissue repair following dermal excisional injuries. hDF-EVs significantly enhanced the proliferation and migration of both fibroblasts and keratinocytes in a coculture system. Transcriptomic analysis revealed that hDF-EVs upregulated genes involved in cell proliferation and cytokine regulation. Integrated miRNA profiling revealed a subset of hDF-EVs-enriched miRNAs that mechanistically orchestrate fibroblast activation through coordinated MAPK, Wnt, and Ras signaling axis engagement, consequently reprogramming inflammatory mediator secretion dynamics in wound microenvironments. Furthermore, cytokine array analysis demonstrated that hDF-EVs enhanced the expression of various cytokines, including Amphiregulin, GCSF, IL-7, and IL-2, while activating Ras, Rap1, PI3K-Akt, and MAPK signaling pathways during the early stage of wound healing. Collectively, hDF-EVs promote wound healing by modulating early growth factor dynamics and enhancing fibroblast-keratinocyte crosstalk, presenting a novel cell-free strategy for skin regeneration.</p>","PeriodicalId":9806,"journal":{"name":"Cell Biology International","volume":" ","pages":""},"PeriodicalIF":3.1000,"publicationDate":"2025-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Fibroblast-Derived Extracellular Vesicles Ameliorate the Skin Injury Microenvironment to Promote Wound Healing.\",\"authors\":\"Minjie Liu, Ganqin Ye, Ruiyang Li, Tenghui Gao, Caiwei Zhuang, Shiyun Huang, Sheng Wang, Jinhua Hu, Andy Peng Xiang, Mei Hua Jiang\",\"doi\":\"10.1002/cbin.70063\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Fibroblasts are pivotal cellular components in cutaneous wound healing and are regarded as promising therapeutic candidates. However, their functional heterogeneity within tissue microenvironments significantly limits their clinical application. In contrast, whether fibroblast-derived extracellular vesicles (EVs) can overcome fibroblast heterogeneity while retaining the bioactivity and regenerative potential of homeostatic fibroblasts remains unclear. In this study, we systematically analyzed and compared the therapeutic potential and functional advantages of human dermal fibroblast-derived EVs (hDF-EVs) in promoting cutaneous wound healing. Our findings highlight the translational potential of fibroblast-derived EVs as a novel strategy to improve clinical outcomes for skin injuries. hDF-EVs were internalized by fibroblasts and keratinocytes at the wound margins, thereby attenuating early inflammatory responses and accelerating tissue repair following dermal excisional injuries. hDF-EVs significantly enhanced the proliferation and migration of both fibroblasts and keratinocytes in a coculture system. Transcriptomic analysis revealed that hDF-EVs upregulated genes involved in cell proliferation and cytokine regulation. Integrated miRNA profiling revealed a subset of hDF-EVs-enriched miRNAs that mechanistically orchestrate fibroblast activation through coordinated MAPK, Wnt, and Ras signaling axis engagement, consequently reprogramming inflammatory mediator secretion dynamics in wound microenvironments. Furthermore, cytokine array analysis demonstrated that hDF-EVs enhanced the expression of various cytokines, including Amphiregulin, GCSF, IL-7, and IL-2, while activating Ras, Rap1, PI3K-Akt, and MAPK signaling pathways during the early stage of wound healing. 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Fibroblast-Derived Extracellular Vesicles Ameliorate the Skin Injury Microenvironment to Promote Wound Healing.
Fibroblasts are pivotal cellular components in cutaneous wound healing and are regarded as promising therapeutic candidates. However, their functional heterogeneity within tissue microenvironments significantly limits their clinical application. In contrast, whether fibroblast-derived extracellular vesicles (EVs) can overcome fibroblast heterogeneity while retaining the bioactivity and regenerative potential of homeostatic fibroblasts remains unclear. In this study, we systematically analyzed and compared the therapeutic potential and functional advantages of human dermal fibroblast-derived EVs (hDF-EVs) in promoting cutaneous wound healing. Our findings highlight the translational potential of fibroblast-derived EVs as a novel strategy to improve clinical outcomes for skin injuries. hDF-EVs were internalized by fibroblasts and keratinocytes at the wound margins, thereby attenuating early inflammatory responses and accelerating tissue repair following dermal excisional injuries. hDF-EVs significantly enhanced the proliferation and migration of both fibroblasts and keratinocytes in a coculture system. Transcriptomic analysis revealed that hDF-EVs upregulated genes involved in cell proliferation and cytokine regulation. Integrated miRNA profiling revealed a subset of hDF-EVs-enriched miRNAs that mechanistically orchestrate fibroblast activation through coordinated MAPK, Wnt, and Ras signaling axis engagement, consequently reprogramming inflammatory mediator secretion dynamics in wound microenvironments. Furthermore, cytokine array analysis demonstrated that hDF-EVs enhanced the expression of various cytokines, including Amphiregulin, GCSF, IL-7, and IL-2, while activating Ras, Rap1, PI3K-Akt, and MAPK signaling pathways during the early stage of wound healing. Collectively, hDF-EVs promote wound healing by modulating early growth factor dynamics and enhancing fibroblast-keratinocyte crosstalk, presenting a novel cell-free strategy for skin regeneration.
期刊介绍：
Each month, the journal publishes easy-to-assimilate, up-to-the minute reports of experimental findings by researchers using a wide range of the latest techniques. Promoting the aims of cell biologists worldwide, papers reporting on structure and function - especially where they relate to the physiology of the whole cell - are strongly encouraged. Molecular biology is welcome, as long as articles report findings that are seen in the wider context of cell biology. In covering all areas of the cell, the journal is both appealing and accessible to a broad audience. Authors whose papers do not appeal to cell biologists in general because their topic is too specialized (e.g. infectious microbes, protozoology) are recommended to send them to more relevant journals. Papers reporting whole animal studies or work more suited to a medical journal, e.g. histopathological studies or clinical immunology, are unlikely to be accepted, unless they are fully focused on some important cellular aspect.
These last remarks extend particularly to papers on cancer. Unless firmly based on some deeper cellular or molecular biological principle, papers that are highly specialized in this field, with limited appeal to cell biologists at large, should be directed towards journals devoted to cancer, there being very many from which to choose.
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