Melatonin treatment improves adipose‐derived mesenchymal stem cell therapy for acute lung ischemia–reperfusion injury |
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Authors: | Christopher Glenn Wallace Li‐Teh Chang Tzu‐Hsien Tsai Yung‐Lung Chen Hsueh‐Wen Chang Steve Leu Yen‐Yi Zhen Ching‐Yen Tsai Kuo‐Ho Yeh Cheuk‐Kwan Sun Chia‐Hung Yen |
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Institution: | 1. Department of Plastic Surgery, University Hospital of South Manchester, , Manchester, UK;2. Nursing Department, Basic Science, Meiho University, , Pingtung, Taiwan;3. Division of Cardiology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, , Kaohsiung, Taiwan;4. Department of Biological Sciences, National Sun Yat‐Sen University, , Kaohsiung, Taiwan;5. Center for Translational Research in Biomedical Sciences, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, , Kaohsiung, Taiwan;6. Institute of Molecular Biology, Academia Sinica, , Taipei, Taiwan;7. Department of Emergency Medicine, E‐DA Hospital, I‐Shou University, , Kaohsiung, Taiwan;8. Department of Biological Science and Technology, National Pingtung University of Science and Technology, , Pingtung, Taiwan |
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Abstract: | This study investigated whether melatonin‐treated adipose‐derived mesenchymal stem cells (ADMSC) offered superior protection against acute lung ischemia–reperfusion (IR) injury. Adult male Sprague‐Dawley rats (n = 30) were randomized equally into five groups: sham controls, lung IR–saline, lung IR–melatonin, lung IR–melatonin–normal ADMSC, and lung IR–melatonin–apoptotic ADMSC. Arterial oxygen saturation was lowest in lung IR–saline; lower in lung IR–melatonin than sham controls, lung IR–melatonin–normal ADMSC, and lung IR–melatonin–apoptotic ADMSC; lower in lung IR–melatonin–normal ADMSC than sham controls and lung IR–melatonin–apoptotic ADMSC; lower in lung IR–melatonin–apoptotic ADMSC than sham controls (P < 0.0001 in each case). Right ventricular systolic blood pressure (RVSBP) showed a reversed pattern among all groups (all P < 0.0001). Changes in histological scoring of lung parenchymal damage and CD68+ cells showed a similar pattern compared with RVSBP in all groups (all P < 0.001). Changes in inflammatory protein expressions such as VCAM‐1, ICAM‐1, oxidative stress, TNF‐α, NF‐κB, PDGF, and angiotensin II receptor, and changes in apoptotic protein expressions of cleaved caspase 3 and PARP, and mitochondrial Bax, displayed identical patterns compared with RVSBP in all groups (all P < 0.001). Numbers of antioxidant (GR+, GPx+, NQO‐1+) and endothelial cell biomarkers (CD31+ and vWF+) were lower in sham controls, lung IR–saline, and lung IR–melatonin than lung IR–melatonin–normal ADMSC and lung IR–melatonin–apoptotic ADMSC, and lower in lung IR–melatonin–normal ADMSC than lung IR–melatonin–apoptotic ADMSC (P < 0.001 in each case). In conclusion, when the animals were treated with melatonin, the apoptotic ADMSC were superior to normal ADMSC for protection of lung from acute IR injury. |
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Keywords: | acute ischemia– reperfusion lung injury adipose‐derived mesenchymal stem cells inflammation melatonin oxidative stress |
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