title: Adipose-derived mesenchymal stem cell protects kidneys against ischemia-reperfusion injury through suppressing oxidative stress and inflammatory reaction.
abstract: BACKGROUND
  Reactive oxygen species are important mediators exerting toxic effects on various organs during ischemia-reperfusion (IR) injury. We hypothesized that adipose-derived mesenchymal stem cells (ADMSCs) protect the kidney against oxidative stress and inflammatory stimuli in rat during renal IR injury.
  
  
  METHODS
  Adult male Sprague-Dawley (SD) rats (n = 24) were equally randomized into group 1 (sham control), group 2 (IR plus culture medium only), and group 3 (IR plus immediate intra-renal administration of 1.0 × 106 autologous ADMSCs, followed by intravenous ADMSCs at 6 h and 24 h after IR). The duration of ischemia was 1 h, followed by 72 hours of reperfusion before the animals were sacrificed.
  
  
  RESULTS
  Serum creatinine and blood urea nitrogen levels and the degree of histological abnormalities were markedly lower in group 3 than in group 2 (all p < 0.03). The mRNA expressions of inflammatory, oxidative stress, and apoptotic biomarkers were lower, whereas the anti-inflammatory, anti-oxidative, and anti-apoptotic biomarkers were higher in group 3 than in group 2 (all p < 0.03). Immunofluorescent staining showed a higher number of CD31+, von Willebrand Factor+, and heme oxygenase (HO)-1+ cells in group 3 than in group 2 (all p < 0.05). Western blot showed notably higher NAD(P)H quinone oxidoreductase 1 and HO-1 activities, two indicators of anti-oxidative capacity, in group 3 than those in group 2 (all p < 0.04). Immunohistochemical staining showed higher glutathione peroxidase and glutathione reductase activities in group 3 than in group 2 (all p < 0.02)
  
  
  CONCLUSIONS
  ADMSC therapy minimized kidney damage after IR injury through suppressing oxidative stress and inflammatory response.
authors.affiliation: Division of Cardiology, Department of Internal Medicine, Chang Gung Memorial Hospital-Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan.
authors.forename: Yen-Ta
authors.initials: YT
authors.lastname: Chen
authors.forename: Cheuk-Kwan
authors.initials: CK
authors.lastname: Sun
authors.forename: Yu-Chun
authors.initials: YC
authors.lastname: Lin
authors.forename: Li-Teh
authors.initials: LT
authors.lastname: Chang
authors.forename: Yung-Lung
authors.initials: YL
authors.lastname: Chen
authors.forename: Tzu-Hsien
authors.initials: TH
authors.lastname: Tsai
authors.forename: Sheng-Ying
authors.initials: SY
authors.lastname: Chung
authors.forename: Sarah
authors.initials: S
authors.lastname: Chua
authors.forename: Ying-Hsien
authors.initials: YH
authors.lastname: Kao
authors.forename: Chia-Hong
authors.initials: CH
authors.lastname: Yen
authors.forename: Pei-Lin
authors.initials: PL
authors.lastname: Shao
authors.forename: Kuan-Cheng
authors.initials: KC
authors.lastname: Chang
authors.forename: Steve
authors.initials: S
authors.lastname: Leu
authors.forename: Hon-Kan
authors.initials: HK
authors.lastname: Yip
mesh_terms: D000273:Adipose Tissue / Q000166:cytology*; D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D017209:Apoptosis / Q000235:genetics; D001806:Blood Urea Nitrogen; D003404:Creatinine / Q000097:blood / Q000652:urine; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D005786:Gene Expression Regulation; D007249:Inflammation / Q000150:complications / Q000235:genetics / Q000517:prevention & control*; D007668:Kidney / Q000378:metabolism / Q000473:pathology*; D007684:Kidney Tubules / Q000378:metabolism / Q000473:pathology; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D018384:Oxidative Stress / Q000235:genetics; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000097:blood / Q000473:pathology / Q000517:prevention & control* / Q000652:urine; D014841:von Willebrand Factor / Q000378:metabolism
chemical_list: D000975:Antioxidants; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D012333:RNA, Messenger; D014841:von Willebrand Factor; D003404:Creatinine