title: Melatonin treatment improves adipose-derived mesenchymal stem cell therapy for acute lung ischemia-reperfusion injury.
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.
authors.affiliation: Division of Cardiology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan.
authors.forename: Hon-Kan
authors.initials: HK
authors.lastname: Yip
authors.forename: Yi-Chih
authors.initials: YC
authors.lastname: Chang
authors.forename: Christopher Glenn
authors.initials: CG
authors.lastname: Wallace
authors.forename: Li-Teh
authors.initials: LT
authors.lastname: Chang
authors.forename: Tzu-Hsien
authors.initials: TH
authors.lastname: Tsai
authors.forename: Yung-Lung
authors.initials: YL
authors.lastname: Chen
authors.forename: Hsueh-Wen
authors.initials: HW
authors.lastname: Chang
authors.forename: Steve
authors.initials: S
authors.lastname: Leu
authors.forename: Yen-Yi
authors.initials: YY
authors.lastname: Zhen
authors.forename: Ching-Yen
authors.initials: CY
authors.lastname: Tsai
authors.forename: Kuo-Ho
authors.initials: KH
authors.lastname: Yeh
authors.forename: Cheuk-Kwan
authors.initials: CK
authors.lastname: Sun
authors.forename: Chia-Hung
authors.initials: CH
authors.lastname: Yen
mesh_terms: D000273:Adipose Tissue / Q000166:cytology*; D050154:Adiposity / Q000502:physiology; D000818:Animals; D015153:Blotting, Western; D007150:Immunohistochemistry; D008297:Male; D008550:Melatonin / Q000627:therapeutic use*; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000188:drug therapy* / Q000628:therapy*; D033581:Stem Cell Transplantation
chemical_list: D008550:Melatonin