title: Systemic administration of autologous adipose-derived mesenchymal stem cells alleviates hepatic ischemia-reperfusion injury in rats.
abstract: OBJECTIVE
  Mesenchymal stem cells have previously been shown to offer significant therapeutic benefit in ischemic organ injuries. This study aimed at investigating the therapeutic role of adipose tissue-derived mesenchymal stem cells in hepatic ischemia-reperfusion injury and the underlying mechanisms.
  
  
  METHODS
  Adult male Fisher rats (n = 30) were equally divided into three groups (group 1: Sham-operated normal controls; group 2: Ischemia-reperfusion injury with intravenous fresh culture medium; group 3: Ischemia-reperfusion injury with intravenous adipose tissue-derived mesenchymal stem cells). Ischemia-reperfusion injury was induced by occluding the vascular supplies of left lobe liver for 60 minutes followed by reperfusion for 72 hrs. Adipose tissue-derived mesenchymal stem cells (1.2 × 106) were administered through tail vein immediately after reperfusion and at 6 hrs and 24 hrs after reperfusion in group 3. All animals were sacrificed 72 hrs after reperfusion.
  
  
  METHODS
  Animal laboratory at a medical institute.
  
  
  RESULTS
  Histologic features, plasma aspartate aminotransferase, hepatic cytokine profile, oxidative stress, and terminal deoxynucleotidyltransferase-mediated dUTP nick end labeling were analyzed. Seventy-two hrs after reperfusion, plasma aspartate aminotransferase, hepatic oxidative stress, messenger RNA expressions of tumor necrosis factor-a, transforming growth factor-b, interleukin-1b, interleukin-6, endothelin-1, matrix metalloproteinase-9, plasminogen activator inhibitor-1, Bax and caspase-3, protein expression of intercellular adhesion molecule as well as the number of apoptotic nuclei were significantly increased in group 2 compared with group 3, whereas messenger RNA expressions of endothelial nitric oxide synthase, Bcl-2, interleukin-10, protein expressions of reduced nicotinamide-adenine dinucleotide phosphate:quinone oxidoreductase 1, and heme oxygenase-1 were lower in group 2 than group 3.
  
  
  CONCLUSIONS
  The results showed that systemic adipose tissue-derived mesenchymal stem cell administration significantly preserved hepatocyte integrity and suppressed inflammatory responses, oxidative stress, and apoptosis in a rodent model of hepatic ischemia-reperfusion injury.
authors.affiliation: Department of Emergency Medicine, E-Da Hospital, I-Shou University, Kaohsiung, Taiwan.
authors.forename: Cheuk-Kwan
authors.initials: CK
authors.lastname: Sun
authors.forename: Chia-Lo
authors.initials: CL
authors.lastname: Chang
authors.forename: Yu-Chun
authors.initials: YC
authors.lastname: Lin
authors.forename: Ying-Hsien
authors.initials: YH
authors.lastname: Kao
authors.forename: Li-Teh
authors.initials: LT
authors.lastname: Chang
authors.forename: Chia-Hung
authors.initials: CH
authors.lastname: Yen
authors.forename: Pei-Lin
authors.initials: PL
authors.lastname: Shao
authors.forename: Chih-Hung
authors.initials: CH
authors.lastname: Chen
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; D017209:Apoptosis; D015153:Blotting, Western; D015815:Cell Adhesion Molecules / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D005434:Flow Cytometry; D020287:In Situ Nick-End Labeling; D007249:Inflammation / Q000517:prevention & control; D008099:Liver / Q000473:pathology; D008107:Liver Diseases / Q000628:therapy*; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods; D018384:Oxidative Stress; D051381:Rats; D011916:Rats, Inbred F344; D060888:Real-Time Polymerase Chain Reaction; D015427:Reperfusion Injury / Q000473:pathology / Q000628:therapy*
chemical_list: D015815:Cell Adhesion Molecules; D016207:Cytokines