title: Protection against acetaminophen-induced acute liver failure by omentum adipose tissue derived stem cells through the mediation of Nrf2 and cytochrome P450 expression.
abstract: BACKGROUND
  Acetaminophen (APAP) overdose causes acute liver failure (ALF) in animals and humans via the rapid depletion of intracellular glutathione (GSH) and the generation of excess reactive oxygen species (ROS) that damage hepatocytes. Stem cell therapy is a potential treatment strategy for ALF.
  
  
  METHODS
  We isolated mesenchymal stem cells (MSCs) from mice omentum adipose tissue-derived stem cells (ASCs) and transplanted them into a mouse model of APAP-induced ALF to explore their therapeutic potential. In addition, we performed in vitro co-culture studies with omentum-derived ASCs and primary isolated hepatocytes to demonstrate the hepatoprotective effect of omentum-derived ASCs on hepatocytes that were subjected to APAP-induced damage.
  
  
  RESULTS
  ASC transplantation significantly improved the survival rate of mice with ALF and attenuated the severity of APAP-induced liver damage by suppressing cytochrome P450 activity to reduce the accumulation of toxic nitrotyrosine and the upregulation of NF-E2-related factor 2 (Nrf2) expression, resulting in an increase in the subsequent antioxidant activity. These effects protected the hepatocytes from APAP-induced damage through the suppression of downstream MAPK signal activation and inflammatory cytokine production.
  
  
  CONCLUSIONS
  our results demonstrate that omentum-derived ASCs are an alternative source of ASCs that regulate the antioxidant response and may represent a beneficial therapeutic strategy for ALF.
authors.affiliation: Institute of Biotechnology, College of Bioresources and Agriculture, National Taiwan University, Taipei, Taiwan. jenhuang456@gmail.com.|Department of Surgery, National Taiwan University Hospital, Taipei, Taiwan. jenhuang456@gmail.com.
authors.forename: Yu-Jen
authors.initials: YJ
authors.lastname: Huang
authors.affiliation: Department of Surgery, National Taiwan University Hospital Yun-Lin Branch, Yunlin, Taiwan. podachen@gmail.com.
authors.forename: Poda
authors.initials: P
authors.lastname: Chen
authors.affiliation: Department of Surgery, National Taiwan University Hospital, Taipei, Taiwan. gs2119@gmail.com.
authors.forename: Chih-Yuan
authors.initials: CY
authors.lastname: Lee
authors.affiliation: Department of Surgery, National Taiwan University Hospital, Taipei, Taiwan. jessica0324777@gmail.com.
authors.forename: Sin-Yu
authors.initials: SY
authors.lastname: Yang
authors.affiliation: Department of Surgery, National Taiwan University Hospital, Taipei, Taiwan. linmt@ntu.edu.tw.|Department of Medicine Education & Bioethics Graduate Institute of Medical Education, Bioethics National Taiwan University College of Medicine, Taipei, Taiwan. linmt@ntu.edu.tw.
authors.forename: Ming-Tsan
authors.initials: MT
authors.lastname: Lin
authors.affiliation: Institute of Biotechnology, College of Bioresources and Agriculture, National Taiwan University, Taipei, Taiwan. benlee@ntu.edu.tw.|Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan. benlee@ntu.edu.tw.
authors.forename: Hsuan-Shu
authors.initials: HS
authors.lastname: Lee
authors.affiliation: Department of Surgery, National Taiwan University Hospital, Taipei, Taiwan. wyaoming@gmail.com.|Department of Surgery, National Taiwan University College of Medicine, Taipei, Taiwan. wyaoming@gmail.com.
authors.forename: Yao-Ming
authors.initials: YM
authors.lastname: Wu
mesh_terms: D000082:Acetaminophen / Q000009:adverse effects* / Q000494:pharmacology; D000273:Adipose Tissue / Q000378:metabolism*; D000818:Animals; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis*; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D017114:Liver Failure, Acute / Q000139:chemically induced / Q000378:metabolism / Q000517:prevention & control; D008297:Male; D051379:Mice; D051267:NF-E2-Related Factor 2 / Q000378:metabolism*; D009852:Omentum / Q000378:metabolism*; D033581:Stem Cell Transplantation; D013234:Stem Cells / Q000378:metabolism*
chemical_list: D051267:NF-E2-Related Factor 2; C495636:Nfe2l2 protein, mouse; D000082:Acetaminophen; D003577:Cytochrome P-450 Enzyme System