Mesenchymal Stem Cell-Derived Extracellular Vesicles Attenuate Radiation-Induced Lung Injury via miRNA-214-3p

间充质干细胞衍生的细胞外囊泡通过 miRNA-214-3p 减轻放射性肺损伤

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作者:Xudan Lei, Ningning He, Lihong Zhu, Manqian Zhou, Kaiyue Zhang, Chen Wang, Haoyan Huang, Shang Chen, Yuhao Li, Qiang Liu, Zhibo Han, Zhikun Guo, Zhongchao Han, Zongjin Li

Aims

Radiotherapy is an effective treatment for thoracic malignancies, but it can cause pulmonary injury and may lead to respiratory failure in a subset of patients. Extracellular vesicles (EVs) derived from mesenchymal stem cells (MSCs) are now recognized as a new candidate for cell-free treatment of lung diseases. Here, we investigated whether MSC-derived EVs (MSC-EVs) could ameliorate radiation-induced lung injury.

Conclusion

Our study reveals that MSC-EVs can reduce pulmonary radiation injury through transferring miR-214-3p, providing new avenues to minimize lung injury from radiation therapy. Antioxid. Redox Signal. 35, 849-862.

Results

We exposed mice to thoracic radiation with a total dose of 15 Gy and assessed the protective effects of MSC-EVs on endothelial cells damage, vascular permeability, inflammation, and fibrosis. We found that MSC-EVs attenuated radiation-induced lung vascular damage, inflammation, and fibrosis. Moreover, MSC-EVs reduced the levels of radiation-induced DNA damage by downregulating ATM/P53/P21 signaling. Our results confirmed that the downregulation of ataxia telangiectasia mutated (ATM) was regulated by miR-214-3p, which was enriched in MSC-EVs. Further analysis demonstrated that MSC-EVs inhibited the senescence-associated secretory phenotype development and attenuated the radiation-induced injury of endothelial cells. Innovation and

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