Hu YL, Lin ZX, Zhang XY, Li GL, Liu WJ, Shi ZQ, Li XH, Yang ZZ. Combining mitochondrial antioxidant mitoquinone and mesenchymal stem cell therapy for amelioration of radiation-induced lung injury: Synergistic regenerative strategy. World J Stem Cells 2026; 18(6): 117622 [DOI: 10.4252/wjsc.117622]
Corresponding Author of This Article
Zhen-Zhou Yang, MD, Department of Cancer Center, The Second Affiliated Hospital of Chongqing Medical University, No. 74 Linjiang Road, Chongqing 400000, China. yangzz@cqmu.edu.cn
Research Domain of This Article
Cell Biology
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research-article
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Hu YL, Lin ZX, Zhang XY, Li GL, Liu WJ, Shi ZQ, Li XH, Yang ZZ. Combining mitochondrial antioxidant mitoquinone and mesenchymal stem cell therapy for amelioration of radiation-induced lung injury: Synergistic regenerative strategy. World J Stem Cells 2026; 18(6): 117622 [DOI: 10.4252/wjsc.117622]
Yan-Ling Hu, Xiao-Yue Zhang, Wei-Jie Liu, Zhen-Zhou Yang, Department of Cancer Center, The Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, China
Yan-Ling Hu, Guo-Li Li, Wei-Jie Liu, Zhong-Quan Shi, Xiao-Han Li, Department of Basic Medicine, Chongqing Three Gorges Medical College, Chongqing 404120, China
Zhong-Xiang Lin, Academic Affairs Office, Chongqing Three Gorges Medical College, Chongqing 404120, China
Co-first authors: Yan-Ling Hu and Zhong-Xiang Lin.
Author contributions: Hu YL and Lin ZX conceived and designed the study, they contributed equally to this manuscript and are co-first authors; Hu YL, Zhang XY, Li GL, and Liu WJ conducted experiments and collected data; Hu YL, Lin ZX, Zhang XY, Li GL, Liu WJ, Shi ZQ, and Li XH analyzed and interpreted the data; Hu YL, Lin ZX, and Yang ZZ drafted the manuscript; and all authors critically revised the manuscript and approved the final version.
Institutional animal care and use committee statement: All animal experimental procedures were reviewed and approved by the Institutional Animal Care and Use Committee of Chongqing Three Gorges Medical College (Approval No. CQ-JL-2023090105).
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 generated and analyzed during this study are available from the corresponding author upon reasonable request. No additional data are available beyond those reported in this article.
Corresponding author: Zhen-Zhou Yang, MD, Department of Cancer Center, The Second Affiliated Hospital of Chongqing Medical University, No. 74 Linjiang Road, Chongqing 400000, China. yangzz@cqmu.edu.cn
Received: January 20, 2026 Revised: February 7, 2026 Accepted: March 30, 2026 Published online: June 26, 2026 Processing time: 155 Days and 23.4 Hours
Abstract
BACKGROUND
Radiation-induced lung injury (RILI) is a major dose-limiting complication of thoracic radiotherapy. Its progression is driven by oxidative stress imbalance, mitochondrial dysfunction, inflammatory amplification, and fibroblast activation. Growing evidence indicates that mitochondrial reactive oxygen species (ROS) accumulation and disruption of mitochondrial quality control are early triggers of epithelial injury and cGAS-STING-mediated inflammation. Mesenchymal stem cells (MSCs) exhibit anti-inflammatory and antifibrotic properties but demonstrate poor survival in highly oxidative microenvironments. Mitoquinone (MitoQ), a mitochondria-targeted antioxidant, effectively scavenges mitochondrial ROS and restores mitochondrial homeostasis. Combining MitoQ with MSCs may enhance MSC viability and therapeutic efficacy.
AIM
To evaluate the synergistic therapeutic effects and underlying mechanisms of MitoQ combined with MSCs in treating RILI.
METHODS
Eighty C57BL/6 mice with RILI were randomly assigned to four groups (n = 20 per group): Model, MitoQ, MSCs, and combination (MitoQ combined with MSCs). Lung function [airway resistance (Raw) and respiratory system compliance (Crs)], oxidative stress (ROS, malondialdehyde, and glutathione), mitochondrial function (JC-1 red/green ratio and ATP), and histopathology were systematically assessed.
RESULTS
Compared with the model group, MitoQ, MSCs, and especially their combination significantly improved pulmonary function and reduced oxidative stress, mitochondrial damage, fibrosis, and inflammation in radiation-induced lung injury (all P < 0.05). The combination group showed lower airway resistance, higher respiratory compliance, lower ROS and malondialdehyde levels, and higher glutathione levels than either monotherapy group. It also exhibited better mitochondrial membrane potential, ATP production, and ultrastructural preservation. In addition, collagen deposition, α-smooth muscle actin and transforming growth factor-β1 expression, and inflammatory scores were further reduced by combination therapy. Correlation and logistic regression analyses indicated that oxidative stress, mitochondrial dysfunction, and profibrotic factors were closely associated with disease progression.
CONCLUSION
MitoQ plus MSCs synergistically alleviated RILI by reducing mitochondrial oxidative stress, restoring mitochondrial function, and suppressing inflammation-fibrosis progression, improving stem cell therapeutic efficacy for RILI.
Core Tip: Radiation-induced lung injury (RILI) remains a major limitation in thoracic radiotherapy, driven by oxidative stress, mitochondrial dysfunction, and inflammation-fibrosis progression. Mesenchymal stem cells offer therapeutic potential but have limited survival in oxidative environments. This study demonstrates that combining the mitochondria-targeted antioxidant mitoquinone with mesenchymal stem cells significantly enhances treatment efficacy in a murine RILI model. The combination therapy improved lung function, reduced oxidative stress, restored mitochondrial homeostasis, and attenuated inflammation and fibrosis more effectively than either monotherapy. These findings highlight a dual-target strategy that optimizes stem cell-based interventions, offering a promising approach for RILI management.
