Manganese Superoxide Dismutase Gene-Modified Mesenchymal Stem Cells Attenuate Acute Radiation-Induced Lung Injury.
Radiation-induced lung injury (RILI) is a major clinical complication for radiotherapy in thoracic tumors. An immediate effect of lung irradiation is the generation of reactive oxygen that can produce oxidative damage to DNA, lipids, and proteins resulting in lung cell injury or death. Currently, the medical management of RILI remains supportive. Therefore, there is an urgent need for the development of countermeasures. The present study aimed to evaluate the protective effect of manganese superoxide dismutase (MnSOD) gene-modified mesenchymal stem cells (MSCs) to facilitate the improved recovery of RILI. Here, nonobese diabetic/severe combined immunodeficiency mice received a 13 Gy dose of whole-thorax irradiation, and were then transfused intravenously with MnSOD-MSCs and monitored for 30 days. Lung histopathologic analysis, plasma levels of inflammatory cytokines (interleukin [IL]-1, IL-6, IL-10, and tumor necrosis factor-α), profibrotic factor transforming growth factor-β1, and the oxidative stress factor (hydroxyproline) were evaluated after MnSOD-MSC transplant. Apoptotic rates were evaluated by terminal deoxynucleotidyl transferase-mediated nick-end labeling immunohistochemical method. Colonization and differentiation of MnSOD-MSCs in the irradiated lung were analyzed by immunofluorescence staining. Consequently, systemic administration of MnSOD-MSCs significantly attenuated lung inflammation, ameliorated lung damage, and protected the lung cells from apoptosis. MnSOD-MSCs could differentiate into epithelial-like cells in vivo. MnSOD-MSCs were effective in modulating RILI in mice and had great potential for accelerating from bench to bedside.
1 Core Laboratory of Translational Medicine, Institute of Geriatrics, Health Management Institute, Gastrointestinal Department of Southern Building, Laboratory of Basic Research and Translational Medicine for Chronic Heart Failure, General Hospital of the Chinese People's Liberation Army , Beijing, China.
Hai-Xu
HX
Chen
1 Core Laboratory of Translational Medicine, Institute of Geriatrics, Health Management Institute, Gastrointestinal Department of Southern Building, Laboratory of Basic Research and Translational Medicine for Chronic Heart Failure, General Hospital of the Chinese People's Liberation Army , Beijing, China.
Hang
H
Xiang
1 Core Laboratory of Translational Medicine, Institute of Geriatrics, Health Management Institute, Gastrointestinal Department of Southern Building, Laboratory of Basic Research and Translational Medicine for Chronic Heart Failure, General Hospital of the Chinese People's Liberation Army , Beijing, China.
Wen-Huan
WH
Xu
2 School of Radiation Medicine and Protection, Medical College of Soochow University , Suzhou, China.
Ming
M
Li
3 Departments of Hematology and Blood Transfusion, General Hospital of the PLA Rocket Force , Beijing, China .
Jie
J
Yuan
3 Departments of Hematology and Blood Transfusion, General Hospital of the PLA Rocket Force , Beijing, China .
Juan
J
Liu
3 Departments of Hematology and Blood Transfusion, General Hospital of the PLA Rocket Force , Beijing, China .
Wan-Jun
WJ
Sun
3 Departments of Hematology and Blood Transfusion, General Hospital of the PLA Rocket Force , Beijing, China .
Rong
R
Zhang
3 Departments of Hematology and Blood Transfusion, General Hospital of the PLA Rocket Force , Beijing, China .
Jun
J
Li
3 Departments of Hematology and Blood Transfusion, General Hospital of the PLA Rocket Force , Beijing, China .
Zhao-Qi
ZQ
Ren
1 Core Laboratory of Translational Medicine, Institute of Geriatrics, Health Management Institute, Gastrointestinal Department of Southern Building, Laboratory of Basic Research and Translational Medicine for Chronic Heart Failure, General Hospital of the Chinese People's Liberation Army , Beijing, China.
Xiao-Mei
XM
Zhang
3 Departments of Hematology and Blood Transfusion, General Hospital of the PLA Rocket Force , Beijing, China .
Bin
B
Du
1 Core Laboratory of Translational Medicine, Institute of Geriatrics, Health Management Institute, Gastrointestinal Department of Southern Building, Laboratory of Basic Research and Translational Medicine for Chronic Heart Failure, General Hospital of the Chinese People's Liberation Army , Beijing, China.
Jun
J
Wan
1 Core Laboratory of Translational Medicine, Institute of Geriatrics, Health Management Institute, Gastrointestinal Department of Southern Building, Laboratory of Basic Research and Translational Medicine for Chronic Heart Failure, General Hospital of the Chinese People's Liberation Army , Beijing, China.
Ben-Yan
BY
Wu
1 Core Laboratory of Translational Medicine, Institute of Geriatrics, Health Management Institute, Gastrointestinal Department of Southern Building, Laboratory of Basic Research and Translational Medicine for Chronic Heart Failure, General Hospital of the Chinese People's Liberation Army , Beijing, China.
Qiang
Q
Zeng
1 Core Laboratory of Translational Medicine, Institute of Geriatrics, Health Management Institute, Gastrointestinal Department of Southern Building, Laboratory of Basic Research and Translational Medicine for Chronic Heart Failure, General Hospital of the Chinese People's Liberation Army , Beijing, China.
Kun-Lun
KL
He
1 Core Laboratory of Translational Medicine, Institute of Geriatrics, Health Management Institute, Gastrointestinal Department of Southern Building, Laboratory of Basic Research and Translational Medicine for Chronic Heart Failure, General Hospital of the Chinese People's Liberation Army , Beijing, China.|3 Departments of Hematology and Blood Transfusion, General Hospital of the PLA Rocket Force , Beijing, China .
Chao
C
Yang
D061605:Administration, Intravenous; D000818:Animals; D017209:Apoptosis / Q000235:genetics; D001992:Bronchoalveolar Lavage Fluid; D005720:Gamma Rays / Q000009:adverse effects; D015870:Gene Expression; D017930:Genes, Reporter; D005822:Genetic Vectors / Q000737:chemistry / Q000378:metabolism; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007375:Interleukin-1 / Q000235:genetics / Q000378:metabolism; D016753:Interleukin-10 / Q000235:genetics / Q000378:metabolism; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism; D016086:Lentivirus / Q000235:genetics* / Q000378:metabolism; D008168:Lung / Q000378:metabolism / Q000473:pathology / Q000528:radiation effects; D055370:Lung Injury / Q000209:etiology / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D016513:Mice, SCID; D013482:Superoxide Dismutase / Q000235:genetics* / Q000378:metabolism; D019076:Transgenes; D014183:Transplantation, Heterologous; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism
D007375:Interleukin-1; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D049452:Green Fluorescent Proteins; D013482:Superoxide Dismutase
cell therapy; manganese superoxide dismutase; mesenchymal stem cells; radiation-induced lung injury