title: Human umbilical cord mesenchymal stromal cells rescue mice from acetaminophen-induced acute liver failure.
abstract: OBJECTIVE
  Acute liver failure (ALF), a life-threatening disease characterized by the sudden loss of hepatic function, can occur after an accidental or intentional acetaminophen overdose.
  
  
  METHODS
  With the use of an ALF mouse model, we examined both the preventive and therapeutic potential of intravenously administered human umbilical cord-derived mesenchymal stromal cells (hUCMSCs). Primary hUCMSCs were purified from freshly collected full-term umbilical cords and intravenously transplanted into BALB/c mice either before and after ALF induced by acetaminophen intoxication. We found that hUCMSCs significantly improved survival rates and relative liver weight of mice in both pre-ALF and post-ALF animals. Correspondingly, serum levels of markers that reflect hepatic injury (ie, aspartate aminotransferase, alanine aminotransferase and total bilirubin) were significantly attenuated in the group receiving hUCMSC therapy.
  
  
  RESULTS
  Mechanistically, we found that the protective potential of intravenously administered hUCMSCs was mediated by paracrine pathways that involved antioxidants (glutathione, superoxide dismutase), the reduction of inflammatory agents (tumor necrosis factor-α, interleukin-6) and elevated serum levels of hepatocyte growth factor.
  
  
  CONCLUSIONS
  Through these paracrine effects, intravenously administered hUCMSCs reduced hepatic necrosis/apoptosis and enhanced liver regeneration. Thus, our data demonstrate that intravenously administered hUCMSCs may be useful in the prevention or treatment of acetaminophen-induced ALF.
authors.affiliation: Shenzhen Beike Cell Engineering Research Institute, Yuanxing Science and Technology Building, Nanshan, Shenzhen, PR China.
authors.forename: Zongcai
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Shenzhen Beike Cell Engineering Research Institute, Yuanxing Science and Technology Building, Nanshan, Shenzhen, PR China.
authors.forename: Fanwei
authors.initials: F
authors.lastname: Meng
authors.affiliation: Shenzhen Beike Cell Engineering Research Institute, Yuanxing Science and Technology Building, Nanshan, Shenzhen, PR China.
authors.forename: Chan
authors.initials: C
authors.lastname: Li
authors.affiliation: Shenzhen Beike Cell Engineering Research Institute, Yuanxing Science and Technology Building, Nanshan, Shenzhen, PR China.
authors.forename: Xin
authors.initials: X
authors.lastname: Zhou
authors.affiliation: Shenzhen Beike Cell Engineering Research Institute, Yuanxing Science and Technology Building, Nanshan, Shenzhen, PR China.
authors.forename: Xiaoping
authors.initials: X
authors.lastname: Zeng
authors.affiliation: Shenzhen Beike Cell Engineering Research Institute, Yuanxing Science and Technology Building, Nanshan, Shenzhen, PR China.
authors.forename: Yixin
authors.initials: Y
authors.lastname: He
authors.affiliation: GMR Epigenetics, Palo Alto, California, USA; Department of Pharmacy & Pharmacology, University of Bath, Bath, England.
authors.forename: Randall J
authors.initials: RJ
authors.lastname: Mrsny
authors.affiliation: Shenzhen Beike Cell Engineering Research Institute, Yuanxing Science and Technology Building, Nanshan, Shenzhen, PR China.
authors.forename: Muyun
authors.initials: M
authors.lastname: Liu
authors.affiliation: Shenzhen Beike Cell Engineering Research Institute, Yuanxing Science and Technology Building, Nanshan, Shenzhen, PR China.
authors.forename: Xiang
authors.initials: X
authors.lastname: Hu
authors.affiliation: VA Palo Alto Health Care System, Stanford University Medical School, Palo Alto, California, USA; GMR Epigenetics, Palo Alto, California, USA. Electronic address: jifan@stanford.edu.
authors.forename: Ji-Fan
authors.initials: JF
authors.lastname: Hu
authors.affiliation: Shenzhen Beike Cell Engineering Research Institute, Yuanxing Science and Technology Building, Nanshan, Shenzhen, PR China. Electronic address: litao@beike.cc.
authors.forename: Tao
authors.initials: T
authors.lastname: Li
mesh_terms: D000082:Acetaminophen / Q000008:administration & dosage / Q000633:toxicity*; D061605:Administration, Intravenous; D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D001663:Bilirubin / Q000097:blood; D002454:Cell Differentiation; D002478:Cells, Cultured; D004195:Disease Models, Animal; D006801:Humans; D008099:Liver / Q000378:metabolism* / Q000473:pathology; D017114:Liver Failure, Acute / Q000139:chemically induced / Q000628:therapy*; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000502:physiology*; D008807:Mice, Inbred BALB C; D014470:Umbilical Cord / Q000166:cytology
chemical_list: D000082:Acetaminophen; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D001663:Bilirubin
keywords: acute liver failure; anti-inflammation; antioxidants; apoptosis; hepatic regeneration; umbilical cord mesenchymal stromal cells