Xudan Lei1,2, Ningning He3, Lihong Zhu4, Manqian Zhou5, Kaiyue Zhang1, Chen Wang1, Haoyan Huang1, Shang Chen1, Yuhao Li1, Qiang Liu3, Zhibo Han6,7, Zhikun Guo8, Zhongchao Han6,7, Zongjin Li1,2,9. 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.
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.
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.
Authors: Evan Paul Tracy; Virginia Stielberg; Gabrielle Rowe; Daniel Benson; Sara S Nunes; James B Hoying; Walter Lee Murfee; Amanda Jo LeBlanc Journal: Am J Physiol Heart Circ Physiol Date: 2022-02-18 Impact factor: 4.733
Authors: Jared M May; Uma Shankavaram; Michelle A Bylicky; Sunita Chopra; Kevin Scott; Shannon Martello; Karla Thrall; Jim Axtelle; Naresh Menon; C Norman Coleman; Molykutty J Aryankalayil Journal: Sci Rep Date: 2022-07-19 Impact factor: 4.996