ORIGINAL RESEARCH article
Front. Immunol.
Sec. Inflammation
This article is part of the Research TopicRole of Extracellular Vesicles in InflammationView all 15 articles
Mechanisms Underlying the Role of TNF-α and IL-1β Preconditioned Exosomes Derived from Human Umbilical Cord Mesenchymal Stem Cells in Wound Healing
Provisionally accepted
- Affiliated Hospital of Zunyi Medical University, Zunyi, China
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Wound healing is a complex physiological process in which a moderate inflammatory response facilitates tissue repair, while excessive inflammation may lead to pathological conditions such as chronic wounds and impaired healing. In this study, we investigated the therapeutic potential of exosomes (Exos) derived from human umbilical cord mesenchymal stem cells (hUC-MSCs) preconditioned with the pro-inflammatory cytokines tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β). We successfully extracted and characterized hUC-MSCs derived Exos (hUCMSCs-Exos) and classified them into Exos obtained under normal culture conditions (Con-Exos) and those stimulated by TNF-α+IL-1β obtained Exos (TNF-α+IL-1β-Exos). TNF-α+IL-1β-Exos significantly accelerated wound healing compared to Con-Exos, enhancing collagen deposition and upregulating the angiogenesis marker CD31 by establishing a a murine full-thickness skin defect model in vivo. In vitro, TNF-α+IL-1β-Exos promoted tube formation and proliferation of human umbilical vein endothelial cells (HUVECs), as demonstrated by the 5-ethynyl-2'-deoxyuridine (EdU) assay. MiRNA sequencing and bioinformatics analysis revealed that miR-215-5p was significantly enriched in TNF-α+IL-1β-Exos. Functional studies confirmed that miR-215-5p mimics enhanced HUVECs tubulogenesis and proliferation, whereas inhibitor had minimal effects. Furthermore, in vivo administration of miR-215-5p mimics markedly improved wound healing in mice. Mechanistically, we identified that miR-215-5p activates the WNK1/p-Smad3/VEGF-A signaling axis, promoting angiogenesis and facilitating cutaneous wound repair. These findings highlight a novel therapeutic strategy for wound healing.
Keywords: Exosomes, Exosomes sequence, hUC-MSCs, Inflammation, Wound Healing
Received: 25 Sep 2025; Accepted: 26 Jan 2026.
Copyright: © 2026 Zhou, Cao, Shi and Jin. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Wenhu Jin
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