title: Cyclosporine-assisted adipose-derived mesenchymal stem cell therapy to mitigate acute kidney ischemia-reperfusion injury.
abstract: BACKGROUND
  This study tested the hypothesis that cyclosporine (CsA)-supported syngeneic adipose-derived mesenchymal stem cell (ADMSC) therapy offered superior attenuation of acute ischemia-reperfusion (IR) kidney injury to either therapy alone.
  
  
  METHODS
  Adult Sprague-Dawley rats (n = 40) were equally divided into group 1 (sham controls), group 2 (IR injury), group 3 (IR + CsA (20 mg/kg at 1 and 24 hours after procedure)), group 4 (syngeneic ADMSC (1.2×106) at 1, 6 and 24 hours after procedure), and group 5 (IR + CsA-ADMSC).
  
  
  RESULTS
  By 72 hours after the IR procedure, the creatinine level and the ratio of urine protein to creatinine were highest in group 2 and lowest in group 1, and significantly higher in groups 3 and 4 than in group 5 (all P <0.05 for inter-group comparisons), but showed no differences between groups 3 and 4 (P >0.05). The inflammatory biomarkers at mRNA (matrix metalloproteinase-9, RANTES, TNF-α), protein (TNF-α, NF-κB, intercellular adhesion molecule-1, platelet-derived growth factor), and cellular (CD68+) levels of IR kidney showed a similar pattern compared with that of creatinine in all groups (all P <0.05 for inter-group comparisons). The protein expressions of oxidative stress (oxidized protein), reactive oxygen species (NADPH oxidases NOX-1, NOX-2), apoptosis (Bcl-2-associated X protein, caspase-3 and poly(ADP-ribose) polymerase) and DNA damage (phosphorylated H2A histone family member X-positive, proliferating cell nuclear antigen-positive cells) markers exhibited a pattern similar to that of inflammatory mediators amongst all groups (all P <0.05 for inter-group comparisons). Expressions of antioxidant biomarkers at cellular (glutathione peroxidase, glutathione reductase, heme oxygenase-1 (HO-1)) and protein (NADPH dehydrogenase (quinone)-1, HO-1, endothelial nitric oxide synthase) levels, and endothelial progenitor cell markers (C-X-C chemokine receptor type 4-positive, stromal cell-derived factor-1α-positive) were lowest in groups 1 and 2, higher in groups 3 and 4, and highest in group 5 (all P <0.05 for inter-group comparisons).
  
  
  CONCLUSIONS
  Combination therapy using CsA plus ADMSCs offers improved protection against acute IR kidney injury.
authors.forename: Yen-Ta
authors.initials: YT
authors.lastname: Chen
authors.forename: Chih-Chau
authors.initials: CC
authors.lastname: Yang
authors.forename: Yen-Yi
authors.initials: YY
authors.lastname: Zhen
authors.forename: Christopher Glenn
authors.initials: CG
authors.lastname: Wallace
authors.forename: Jenq-Lin
authors.initials: JL
authors.lastname: Yang
authors.forename: Cheuk-Kwan
authors.initials: CK
authors.lastname: Sun
authors.forename: Tzu-Hsien
authors.initials: TH
authors.lastname: Tsai
authors.forename: Jiunn-Jye
authors.initials: JJ
authors.lastname: Sheu
authors.forename: Sarah
authors.initials: S
authors.lastname: Chua
authors.forename: Chia-Lo
authors.initials: CL
authors.lastname: Chang
authors.forename: Chung-Lung
authors.initials: CL
authors.lastname: Cho
authors.forename: Steve
authors.initials: S
authors.lastname: Leu
authors.forename: Hon-Kan
authors.initials: HK
authors.lastname: Yip
mesh_terms: D058186:Acute Kidney Injury / Q000473:pathology / Q000628:therapy*; D000273:Adipose Tissue / Q000166:cytology; D000818:Animals; D001806:Blood Urea Nitrogen; D053148:Caspase 3 / Q000235:genetics / Q000378:metabolism; D064987:Cell- and Tissue-Based Therapy; D003404:Creatinine / Q000097:blood / Q000652:urine; D016572:Cyclosporine / Q000627:therapeutic use*; D004249:DNA Damage; D007668:Kidney / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D018384:Oxidative Stress; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000188:drug therapy / Q000473:pathology / Q000628:therapy*; D013482:Superoxide Dismutase / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000235:genetics / Q000378:metabolism
chemical_list: D014409:Tumor Necrosis Factor-alpha; D051028:bcl-2-Associated X Protein; D016572:Cyclosporine; D003404:Creatinine; D013482:Superoxide Dismutase; D053148:Caspase 3