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Photobiomodulation Facilitates Rat Cutaneous Wound Healing by Promoting Epidermal Stem Cells and Hair Follicle Stem Cells Proliferation

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Tissue Engineering and Regenerative Medicine Aims and scope

Abstract

Background:

Cutaneous wound healing represents a common fundamental phenomenon requiring the participation of cells of distinct types and a major concern for the public. Evidence has confirmed that photobiomodulation (PBM) using near-infrared (NIR) can promote wound healing, but the  cells involved and the precise molecular mechanisms remain elusive.

Methods:

Full-thickness skin defects with a diameter of 1.0 cm were made on the back of rats and randomly divided into the control group, 10 J, 15 J, and 30 J groups. The wound healing rate at days 4, 8, and 12 postoperatively was measured. HE and Masson staining was conducted to reveal the histological characteristics. Immunofluorescence staining was performed to label the epidermal stem cells (ESCs) and hair follicle stem cells (HFSCs). Western blot was performed to detect the expressions of proteins associated with ESCs and HFSCs. Cutaneous wound tissues were collected for RNA sequencing. Gene ontology and the Kyoto Encyclopedia of Genes and Genomes analysis was performed, and the hub genes were identified using CytoHubba and validated by qRT-PCR.

Results:

PBM can promote reepithelialization, extracellular matrix deposition, and wound healing, increase the number of KRT14+/PCNA+ ESCs and KRT15+/PCNA+ HFSCs, and upregulate the protein expression of P63, Krt14, and PCNA. Three hundred and sixty-six differentially expressed genes (DEGs) and 7 hub genes including Sox9, Krt5, Epcam, Cdh1, Cdh3, Dsp, and Pkp3 were identified. These DEGs are enriched in skin development, cell junction, and cadherin binding involved in cell–cell adhesion etc., while these hub genes are related to skin derived stem cells and cell adhesion.

Conclusion:

PBM accelerates wound healing by enhancing reepithelialization through promoting ESCs and HFSCs proliferation and elevating the expression of genes associated with stem cells and cell adhesion. This may provide a valuable alternative strategy to promote wound healing and reepithelialization by modulating the proliferation of skin derived stem cells and regulating genes related to cell adhesion.

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Data availability

The data presented in this study are available on request from all the authors.

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Acknowledgement

This work was supported by Key Research and Development Program of Shaanxi, China (No. 2020SF-179).

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Author notes

  1. Tong Wang, Yajuan Song and Liu Yang have contributed equally to this work.

Authors and Affiliations

  1. Department of Plastic Surgery, Xijing Hospital, Fourth Military Medical University, No. 127 Changle West Road, Xi’an, 710032, Shaanxi Province, China

    Tong Wang, Yajuan Song, Liu Yang, Wei Liu, Yi Shi, Baoqiang Song & Zhou Yu

  2. Shaanxi Institute of Medical Device Quality Inspection, Xi’an, 712046, China

    Zhen’an He

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  1. Tong Wang
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The experimental protocol was approved by the animal experiment ethics committee of the Fourth Military Medical University (Xi’an, China) (Permit no. IACUC-20220302).

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Wang, T., Song, Y., Yang, L. et al. Photobiomodulation Facilitates Rat Cutaneous Wound Healing by Promoting Epidermal Stem Cells and Hair Follicle Stem Cells Proliferation. Tissue Eng Regen Med 21, 65–79 (2024). https://doi.org/10.1007/s13770-023-00601-5

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