Melatonin treatment improves adipose-derived mesenchymal stem cell therapy for acute lung ischemiareperfusion injury

This study investigated whether melatonin-treated adipose-derived mesenchymal stem cells (ADMSC) offered superior protection against acute lung ischemiareperfusion (IR) injury. Adult male Sprague-Dawley rats (n=30) were randomized equally into five groups: sham controls, lung IRsaline, lung IRmelatonin, lung IRmelatoninnormal ADMSC, and lung IRmelatoninapoptotic ADMSC. Arterial oxygen saturation was lowest in lung IRsaline; lower in lung IRmelatonin than sham controls, lung IRmelatoninnormal ADMSC, and lung IRmelatoninapoptotic ADMSC; lower in lung IRmelatoninnormal ADMSC than sham controls and lung IRmelatoninapoptotic ADMSC; lower in lung IRmelatoninapoptotic 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-, NF-B, 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 IRsaline, and lung IRmelatonin than lung IRmelatoninnormal ADMSC and lung IRmelatoninapoptotic ADMSC, and lower in lung IRmelatoninnormal ADMSC than lung IRmelatoninapoptotic 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.