title: Impact of apoptotic adipose-derived mesenchymal stem cells on attenuating organ damage and reducing mortality in rat sepsis syndrome induced by cecal puncture and ligation.
abstract: BACKGROUND
  We tested whether apoptotic adipose-derived mesenchymal stem cells (A-ADMSCs) were superior to healthy (H)-ADMSCs at attenuating organ damage and mortality in sepsis syndrome following cecal ligation and puncture (CLP).
  
  
  METHODS
  Adult male rats were categorized into group 1 (sham control), group 2 (CLP), group 3 [CLP + H-ADMSC administered 0.5, 6, and 18 h after CLP], group 4 [CLP + A-ADMSC administered as per group 3].
  
  
  RESULTS
  Circulating peak TNF-α level, at 6 h, was highest in groups 2 and 3, and higher in group 4 than group 1 (p < 0.0001). Immune reactivity (indicated by circulating and splenic helper-, cytoxic-, and regulatory-T cells) at 24 and 72 h exhibited the same pattern as TNF-α amongst the groups (all p < 0.0001). The mononuclear-cell early and late apoptosis level and organ damage parameters of liver (AST, ALT), kidney (creatinine) and lung (arterial oxygen saturation) also displayed a similar pattern to TNF-α levels (all p < 0.001). Protein levels of inflammatory (TNF-α, MMP-9, NF-κB, ICAM-1), oxidative (oxidized protein) and apoptotic (Bax, caspase-3, PARP) biomarkers were higher in groups 2 and 3 than group 1, whereas anti-apoptotic (Bcl-2) biomarker was lower in groups 2 and 3 than in group 1 but anti-oxidant (GR, GPx, HO-1, NQO-1) showed an opposite way of Bcl-2; these patterns were reversed for group 4 (all p < 0.001). Mortality was highest in group 3 and higher in group 2 than group 4 than group 1 (all p < 0.001).
  
  
  CONCLUSIONS
  A-ADMSC therapy protected major organs from damage and improved prognosis in rats with sepsis syndrome.
authors.affiliation: Division of Colorectal Surgery, Department of Surgery, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan, Republic of China.
authors.forename: Chia-Lo
authors.initials: CL
authors.lastname: Chang
authors.forename: Steve
authors.initials: S
authors.lastname: Leu
authors.forename: Hsin-Ching
authors.initials: HC
authors.lastname: Sung
authors.forename: Yen-Yi
authors.initials: YY
authors.lastname: Zhen
authors.forename: Chung-Lung
authors.initials: CL
authors.lastname: Cho
authors.forename: Angela
authors.initials: A
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: Han-Tan
authors.initials: HT
authors.lastname: Chai
authors.forename: Cheuk-Kwan
authors.initials: CK
authors.lastname: Sun
authors.forename: Chia-Hung
authors.initials: CH
authors.lastname: Yen
authors.forename: Hon-Kan
authors.initials: HK
authors.lastname: Yip
mesh_terms: D000273:Adipose Tissue / Q000166:cytology*; D000818:Animals; D017209:Apoptosis; D015415:Biomarkers / Q000378:metabolism; D001794:Blood Pressure; D001835:Body Weight; D002432:Cecum / Q000473:pathology*; D002462:Cell Membrane / Q000378:metabolism; D005434:Flow Cytometry; D006352:Heart Ventricles / Q000473:pathology; D007249:Inflammation / Q000097:blood / Q000473:pathology; D008026:Ligation; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D009206:Myocardium / Q000473:pathology; D009929:Organ Size; D009928:Organ Specificity; D011677:Punctures; D051381:Rats; D013154:Spleen / Q000276:immunology; D016019:Survival Analysis; D018746:Systemic Inflammatory Response Syndrome / Q000097:blood / Q000503:physiopathology / Q000628:therapy*; D013599:Systole; D013601:T-Lymphocytes / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
chemical_list: D015415:Biomarkers; D014409:Tumor Necrosis Factor-alpha