The first two authors made equal contributions to this study.
Melatonin treatment improves adipose-derived mesenchymal stem cell therapy for acute lung ischemia–reperfusion injury
Article first published online: 30 OCT 2012
© 2012 John Wiley & Sons A/S. Published by Blackwell Publishing Ltd.
Journal of Pineal Research
Volume 54, Issue 2, pages 207–221, March 2013
How to Cite
Yip, H.-K., Chang, Y.-C., Wallace, C. G., Chang, L.-T., Tsai, T.-H., Chen, Y.-L., Chang, H.-W., Leu, S., Zhen, Y.-Y., Tsai, C.-Y., Yeh, K.-H., Sun, C.-K. and Yen, C.-H. (2013), Melatonin treatment improves adipose-derived mesenchymal stem cell therapy for acute lung ischemia–reperfusion injury. Journal of Pineal Research, 54: 207–221. doi: 10.1111/jpi.12020
- Issue published online: 6 FEB 2013
- Article first published online: 30 OCT 2012
- Accepted manuscript online: 8 OCT 2012 05:05AM EST
- Manuscript Accepted: 21 SEP 2012
- Manuscript Received: 8 JUL 2012
- acute ischemia–reperfusion lung injury;
- adipose-derived mesenchymal stem cells;
- oxidative stress
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.