Xia ZY, Wang Y, Shi N, Lu MQ, Deng YX, Qi YJ, Wang XL, Zhao J, Jiang DY. Fetal mice dermal mesenchymal stem cells promote wound healing by inducing M2 type macrophage polarization. World J Stem Cells 2025; 17(2): 101030 [DOI: 10.4252/wjsc.v17.i2.101030]
Corresponding Author of This Article
Du-Yin Jiang, MD, Emergency Medicine Center, The Second Hospital of Shandong University, No. 247 Beiyuan Street, Jinan 250033, Shandong Province, China. jduyin0227@163.com
Research Domain of This Article
Biochemistry & Molecular Biology
Article-Type of This Article
Basic Study
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
World J Stem Cells. Feb 26, 2025; 17(2): 101030 Published online Feb 26, 2025. doi: 10.4252/wjsc.v17.i2.101030
Fetal mice dermal mesenchymal stem cells promote wound healing by inducing M2 type macrophage polarization
Zhen-Yu Xia, Yi Wang, Nian Shi, Mei-Qi Lu, Yun-Xiang Deng, Yong-Jun Qi, Xing-Lei Wang, Jie Zhao, Du-Yin Jiang
Zhen-Yu Xia, Yi Wang, Nian Shi, Mei-Qi Lu, Yun-Xiang Deng, Cheeloo College of Medicine, Shandong University, Jinan 250012, Shandong Province, China
Yong-Jun Qi, Department of Plastic Surgery & Burns, The Second Hospital of Shandong University, Jinan 250033, Shandong Province, China
Xing-Lei Wang, Jie Zhao, Du-Yin Jiang, Emergency Medicine Center, The Second Hospital of Shandong University, Jinan 250033, Shandong Province, China
Co-corresponding authors: Jie Zhao and Du-Yin Jiang.
Author contributions: Xia ZY and Wang Y contributed to the conceptualization of this study; Xia ZY and Shi N took part in the data curation; Xia ZY and Lu MQ participated in the formal analysis of this manuscript; Xia ZY and Deng YX contributed to the methodology; Xia ZY and Qi YJ contributed to the resources; Xia ZY and Wang XL contributed to the software; Xia ZY wrote the original draft; Zhao J and Jiang DY contributed to the writing - review & editing. Zhao J and Jiang DY are co-corresponding of this manuscript. Jiang DY provided guidance on the methodological design; Zhao J and Jiang DY jointly guided the conceptualization of our study, and completed the final revisions and confirmation of the manuscript.
Supported by National Natural Science Foundation of China, No. 81873934; and Jinan Science and Technology Planning Project, No. 202225065.
Institutional animal care and use committee statement: Ethical approval for all animal experiments conducted in this study was granted by the Institutional Animal Care and Use Committee at the Second Hospital of Shandong University (Approval No. KYLL-2023LW013). All animal procedures were carried out in strict accordance with institutional guidelines.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
ARRIVE guidelines statement: The authors have read the ARRIVE guidelines, and the manuscript was prepared and revised according to the ARRIVE guidelines.
Data sharing statement: The datasets used and/or analyzed during the present study are available from the corresponding author on reasonable request.
Open Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Du-Yin Jiang, MD, Emergency Medicine Center, The Second Hospital of Shandong University, No. 247 Beiyuan Street, Jinan 250033, Shandong Province, China. jduyin0227@163.com
Received: September 2, 2024 Revised: December 9, 2024 Accepted: February 7, 2025 Published online: February 26, 2025 Processing time: 174 Days and 17.5 Hours
Abstract
BACKGROUND
Mesenchymal stem cells, found in various tissues, possess significant healing and immunomodulatory properties, influencing macrophage polarization, which is essential for wound repair. However, chronic wounds present significant therapeutic challenges, requiring novel strategies to improve healing outcomes.
AIM
To investigate the potential of fetal dermal mesenchymal stem cells (FDMSCs) in enhancing wound healing through modulation of macrophage polarization, specifically by promoting the M2 phenotype to address inflammatory responses in chronic wounds.
METHODS
FDMSCs were isolated from BalB/C mice and co-cultured with RAW264.7 macrophages to assess their effects on macrophage polarization. Flow cytometry, quantitative reverse transcriptase polymerase chain reaction, and histological analyses were employed to evaluate shifts in macrophage phenotype and wound healing in a mouse model. Statistical analysis was performed using GraphPad Prism.
RESULTS
FDMSCs induced macrophage polarization from the M1 to M2 phenotype, as demonstrated by a reduction in pro-inflammatory markers (inducible nitric oxide synthase, interleukin-6) and an increase in anti-inflammatory markers [mannose receptor (CD206), arginase-1] in co-cultured RAW264.7 macrophages. These shifts were confirmed by flow cytometry. In an acute skin wound model, FDMSC-treated mice exhibited faster wound healing, enhanced collagen deposition, and improved vascular regeneration compared to controls. Significantly higher expression of arginase-1 further indicated an enriched M2 macrophage environment.
CONCLUSION
FDMSCs effectively modulate macrophage polarization from M1 to M2, reduce inflammation, and enhance tissue repair, demonstrating their potential as an immunomodulatory strategy in wound healing. These findings highlight the promising therapeutic application of FDMSCs in managing chronic wounds.
Core Tip: This study investigates the role of fetal dermal mesenchymal stem cells in wound healing by modulating macrophage polarization towards a pro-healing M2 phenotype. Using flow cytometry, reverse transcriptase polymerase chain reaction, and histology, we demonstrate that fetal dermal mesenchymal stem cells promote a reparative immune environment, accelerating wound closure, enhancing collagen deposition, and supporting vascular regeneration in a mouse model.
