The cellular ecosystem of skeletal muscle regeneration: molecular mechanisms, pathological disorders, and potential therapeutic strategies
- 1Jiangsu Key Laboratory of Tissue Engineering and Neuroregeneration, Key Laboratory of Neuroregeneration of Ministry of Education, Co- innovation Center of Neuroregeneration, Medical School of Nantong University, Nantong University, Nantong, 226001, Jiangsu, People's Republic of China
- 2Department of Orthopedics, Changshu Hospital Affiliated to Soochow University, First People's Hospital of Changshu City, Changshu, 215500, Jiangsu, People's Republic of China. [email protected]
- 3Jiangsu Key Laboratory of Tissue Engineering and Neuroregeneration, Key Laboratory of Neuroregeneration of Ministry of Education, Co- innovation Center of Neuroregeneration, Medical School of Nantong University, Nantong University, Nantong, 226001, Jiangsu, People's Republic of China. [email protected]
Abstract
Skeletal muscle regeneration is a highly coordinated physiological process. It relies on the intricate collaboration of a complex cellular ecosystem. This ecosystem includes muscle stem cells, immune cells, stromal cells, vascular cells, neural cells, and the extracellular matrix. Research has recently expanded beyond focusing solely on satellite cells. It now delves into the multi-level regulatory networks within this ecosystem. These networks encompass key signaling pathways, such as Wnt/β-catenin, TGF-β, Hippo/YAP, and AMPK. They also include epigenetic regulation, cellular metabolic reprogramming, and extracellular vesicle-mediated intercellular communication. However, under pathological conditions, this regenerative program is severely impaired. This leads to failed repair, fibrosis, and fatty infiltration, ultimately resulting in loss of muscle function. This review aims to systematically outline recent advances in the field of skeletal muscle regeneration. First, from the perspective of the "cellular ecosystem," we will elaborate on the dynamic behaviors and regulatory mechanisms of various cell types during regeneration. Second, we will dissect the core mechanisms underlying regenerative failures in various pathological states. Third, we will comprehensively evaluate the most promising current intervention strategies. Finally, considering the limitations of current research, we will provide future perspectives. This review aims to systematically integrate existing knowledge and provide a clear roadmap for future research, ultimately offering a robust theoretical foundation and innovative insights for the development of clinical treatments targeting skeletal muscle regenerative disorders.
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BibTeX
@article{gong2026cellular,
title = {{The cellular ecosystem of skeletal muscle regeneration: molecular mechanisms, pathological disorders, and potential therapeutic strategies}},
author = {Jiahuan Gong and XU Hong-yi and Xinlei Yao and Y J Wei and Xia Li and Yuntian Shen and Bingqian Chen and Han Sun},
journal = {Stem Cell Research \& Therapy},
year = {2026},
month = may,
doi = {10.1186/s13287-026-05060-y},
url = {https://doi.org/10.1186/s13287-026-05060-y},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - The cellular ecosystem of skeletal muscle regeneration: molecular mechanisms, pathological disorders, and potential therapeutic strategies
AU - Jiahuan Gong
AU - XU Hong-yi
AU - Xinlei Yao
AU - Y J Wei
AU - Xia Li
AU - Yuntian Shen
AU - Bingqian Chen
AU - Han Sun
PY - 2026
DA - 2026/05/16
JO - Stem Cell Research & Therapy
DO - 10.1186/s13287-026-05060-y
UR - https://doi.org/10.1186/s13287-026-05060-y
AB - Skeletal muscle regeneration is a highly coordinated physiological process. It relies on the intricate collaboration of a complex cellular ecosystem. This ecosystem includes muscle stem cells, immune cells, stromal cells, vascular cells, neural cells, and the extracellular matrix. Research has recently expanded beyond focusing solely on satellite cells. It now delves into the multi-level regulatory networks within this ecosystem. These networks encompass key signaling pathways, such as Wnt/β-catenin, TGF-β, Hippo/YAP, and AMPK. They also include epigenetic regulation, cellular metabolic reprogramming, and extracellular vesicle-mediated intercellular communication. However, under pathological conditions, this regenerative program is severely impaired. This leads to failed repair, fibrosis, and fatty infiltration, ultimately resulting in loss of muscle function. This review aims to systematically outline recent advances in the field of skeletal muscle regeneration. First, from the perspective of the "cellular ecosystem," we will elaborate on the dynamic behaviors and regulatory mechanisms of various cell types during regeneration. Second, we will dissect the core mechanisms underlying regenerative failures in various pathological states. Third, we will comprehensively evaluate the most promising current intervention strategies. Finally, considering the limitations of current research, we will provide future perspectives. This review aims to systematically integrate existing knowledge and provide a clear roadmap for future research, ultimately offering a robust theoretical foundation and innovative insights for the development of clinical treatments targeting skeletal muscle regenerative disorders.
SN - 1757-6512
ER -