Protection against acetaminophen-induced acute liver failure by omentum adipose tissue derived stem cells through the mediation of Nrf2 and cytochrome P450 expression. Issue 1 (December 2016)

• Record Type: Journal Article
• Authors: Huang, Yu-Jen; Chen, Poda; Lee, Chih-Yuan; Yang, Sin-Yu; Lin, Ming-Tsan; Lee, Hsuan-Shu; Wu, Yao-Ming
• Is Part Of: Journal of biomedical science. Volume 23:Issue 1(2016)
• Page Start: 1
• Page End: 12
• Publication Date: 2016-12
• Subjects: Acetaminophen -- Acute liver failure -- Omentum adipose tissue-derived stem cells -- Hepatoprotection; Medical sciences -- Periodicals; 610.28
• DOI: 10.1186/s12929-016-0231-x
• Languages: English
• ISSNs: 1021-7770

Abstract

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. Result 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.