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Research Article | Open Access

Epidermal stem cell-derived exosomes improve wound healing by promoting the proliferation and migration of human skin fibroblasts

Deni Kang1,‡, Xiaoxiang Wang2,‡ , Wentao Chen3,‡, Lujia Mao4, Weiqiang Zhang5, Yan Shi6( ), Julin Xie2 ( ), Ronghua Yang1 ( )
Department of Burn and Plastic Surgery, Guangzhou First People's Hospital, Guangzhou Medical University, 1 Panfu Road, Yuexiu District, Guangzhou City, Guangdong Province, 510180, China
Department of Burns, The First Affiliated Hospital of Sun Yat-Sen University, 58 Zhongshan Second Road, Yuexiu District, Guangzhou City, Guangdong Province, 510062, China
Department of Medical cosmetology, Foshan Second People's Hospital, 78 Weiguo Road, Chancheng District, Foshan City, Guangdong Province, 528000, China
Department of Burn and Plastic Surgery, Guangzhou First People's Hospital, South China University of Technology, 1 Panfu Road, Yuexiu District, Guangzhou City, Guangdong Province, 510180, China
The First Clinical Medical College, Guangdong Medical University, 2 Wenming East Road, Xiashan District, Zhanjiang City, Guangdong Province, 524002, China
Department of Plastic, Medical Center of Burn Plastic and Wound Repair, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, No. 17 Yongwai Zheng Street, Donghu District, Nanchang City, Jiangxi Province, 330006, China

‡Deni Kang, Xiaoxiang Wang and Wentao Chen contributed equally to this work.

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Highlights

• The mechanism by which ESCs-Exo accelerate wound healing may involve promoting the proliferation and migration of HSFBs.

• ESCs-Exo may regulate inflammatory and immune responses by modulating PKN1-cyclin to promote HSFBs proliferation and modulate tumor necrosis factor signaling pathways.

• We found that treating HSFBs with ESCs-Exo effectively increased the ratio of collagen Ⅲ/Ⅰ, promoting the formation of scar-free wounds.

Abstract

Background

Epidermal stem cells (ESCs) are primarily located in the basal layer of the epidermis and play a crucial role in wound healing. ESCs-derived exosomes (ESCs-Exo) are emerging as promising candidates for skin regeneration and wound healing. However, the underlying mechanisms remain unclear. This study aims to investigate the role and mechanisms of ESCs-Exo in promoting the proliferation, migration, and collagen synthesis of human skin fibroblasts (HSFBs).

Methods

This study generated, isolated, and characterized ESC-Exos. The effects of ESCs-Exo on the proliferation of human skin fibroblasts (HSFBs) were detected via Cell Counting Kit-8 (CCK8), 5-Ethynyl-2'-deoxyuridine (EdU), and Proliferating Cell Nuclear Antigen (PCNA) and Marker of Proliferation Ki-67 (MKI67) gene expression methods. The effect of ESCs-Exo on the migration of HSFBs was detected via a transwell assay and a scratch test. The concentrations of collagen secreted by the HSFBs and the mRNAs of the two kinds of collagen expressed by the HSFBs were analyzed. We also analyzed the phosphorylation of Protein Kinase N1 (PKN1) and the expression of cyclins via western blotting. Finally, the effect of ESCs-Exo on wound healing was verified by animal experiments, and the key genes and signaling pathways of ESCs-Exo were excavated by transcriptomic analysis.

Results

Western blotting revealed that the exosomes of ESCs highly expressed established markers such as Alix, CD63, and CD9. ESC-Exos significantly promoted HSFB proliferation and migration in a dose-dependent manner, as well as HSFB collagen synthesis, and effectively increased the ratio of collagen III/I. In addition, bioinformatics analysis showed that the expression of key gene C-X-C motif chemokine ligand 9 was lower in the ESCs-Exo group, which may promote wound healing by regulating PKN1-cyclin and tumor necrosis factor signaling pathways. Animal experiments demonstrated that ESCs-Exo could reduce inflammation and accelerate wound healing.

Conclusions

In this study, we found that ESCs-Exo may improve wound healing by promoting the proliferation and migration of HSFBs.

Keywords

Epidermal stem cellsExosomesWound healingHuman skin fibroblastsSkin regenerationMigrationProliferation

References

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Burns & Trauma
Volume 12,
December 2024
Article number: tkae047
DOI: 10.1093/burnst/tkae047

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Cite this article:
Kang D, Wang X, Chen W, et al. Epidermal stem cell-derived exosomes improve wound healing by promoting the proliferation and migration of human skin fibroblasts. Burns & Trauma, 2024, 12: tkae047. https://doi.org/10.1093/burnst/tkae047

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Received: 16 December 2023
Revised: 16 July 2024
Accepted: 01 August 2024
Published: 10 October 2026
© The Author(s) 2024. Published by Oxford University Press.

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.