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

  • Antioxid Redox Signal. 2021 Oct 10;35(11):849-862. doi: 10.1089/ars.2019.7965.
Xudan Lei  1  2 ,  Ningning He  3 ,  Lihong Zhu  4 ,  Manqian Zhou  5 ,  Kaiyue Zhang  1 ,  Chen Wang  1 ,  Haoyan Huang  1 ,  Shang Chen  1 ,  Yuhao Li  1 ,  Qiang Liu  3 ,  Zhibo Han  6  7 ,  Zhikun Guo  8 ,  Zhongchao Han  6  7 ,  Zongjin Li  1  2  9
Affiliations
  • 1. Lab of Molecular Imaging and Stem Cell Therapy, Nankai University School of Medicine, Tianjin, China.
  • 2. The Key Laboratory of Bioactive Materials, Ministry of Education, The College of Life Science, Nankai University, Tianjin, China.
  • 3. Tianjin Key Laboratory of Radiation Medicine and Molecular Nuclear Medicine, Department of Radiobiology, Institute of Radiation Medicine of Chinese Academy of Medical Science and Peking Union Medical College, Tianjin, China.
  • 4. Department of Gynecologic Oncology, Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing, China.
  • 5. Department of Radiation Oncology, Tianjin Union Medical Center, Tianjin, China.
  • 6. Tianjin Key Laboratory of Engineering Technologies for Cell Pharmaceutical, National Engineering Research Center of Cell Products, AmCellGene Co., Ltd., Tianjin, China.
  • 7. Jiangxi Engineering Research Center for Stem Cell, Shangrao, China.
  • 8. Henan Key Laboratory of Medical Tissue Regeneration, Xinxiang Medical University, Xinxiang, China.
  • 9. State Key Laboratory of Kidney Diseases, Chinese PLA General Hospital, Beijing, China.
PMID: 32664737 DOI: 10.1089/ars.2019.7965
Abstract

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. 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 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.

Keywords
ataxia telangiectasia mutated (ATM); extracellular vesicles; mesenchymal stem cell; miR-214-3p; radiation-induced lung injury.
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