ORIGINAL RESEARCH article
Front. Physiol.
Sec. Cell Physiology
This article is part of the Research TopicMechanical Forces in Health and Disease: A Mechanobiological PerspectiveView all 17 articles
Single-cell Transcriptome Analysis profiles Cellular Dynamics and Transcriptional Changes in Diabetic Wound Tissues following ESWT Treatment
Provisionally accepted
- 1China Medical University, Shenyang, China
- 2Angang general hospital, Anshan, China
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Abstract Diabetic wounds (DWs) remain a major complication of diabetes mellitus, characterized by impaired healing and limited therapeutic options. Extracorporeal shock wave therapy (ESWT), a non-invasive physical modality, has recently shown promise in accelerating chronic wound repair, yet the underlying cellular mechanisms remain poorly understood. Here, we employed single-cell RNA sequencing (scRNA-seq) to construct a comprehensive cellular atlas of DW tissues treated with ESWT, profiling approximately 39,475 cells. Our analysis identified 12 major cell populations, including macrophages, fibroblasts, endothelial cells, keratinocytes, and immune subsets, and revealed widespread transcriptional reprogramming associated with ESWT treatment. ESWT promoted the expansion of reparative macrophages, activated pro-regenerative fibroblast states, and restored angiogenic programs in endothelial cells. Moreover, cell–cell communication analysis revealed that ESWT not only attenuates pro-inflammatory signaling but also activates immune cell communication networks, thereby enhancing T cell, NK cell, and dendritic cell interactions. These changes collectively promote immune regulation and tissue repair, contributing to the restoration of a balanced wound microenvironment. Together, these findings provide a high-resolution single-cell map of ESWT-mediated cellular and molecular alterations in DWs and uncover key cellular pathways contributing to improved tissue repair. This study offers new insights into the mechanisms of ESWT and supports its translational potential as a therapeutic strategy for chronic wound management.
Keywords: diabetic wound, Extracorporeal shock wave therapy, Single Cell RNA sequencing, Endothelial Cells, Microenvironment remodeling
Received: 27 Aug 2025; Accepted: 31 Oct 2025.
Copyright: © 2025 Li, Wang, Wang, Shao, Wang, Xin and Ma. 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: Dongyu Li, 20201032@cmu.edu.cn
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