PMID- 26057841
OWN - NLM
STAT- MEDLINE
DCOM- 20160328
LR  - 20190423
IS  - 2045-2322 (Electronic)
IS  - 2045-2322 (Linking)
VI  - 5
DP  - 2015 Jun 9
TI  - Antioxidant treatment enhances human mesenchymal stem cell anti-stress ability 
      and therapeutic efficacy in an acute liver failure model.
PG  - 11100
LID - 10.1038/srep11100 [doi]
LID - 11100
AB  - One of the major problems influencing the therapeutic efficacy of stem cell 
      therapy is the poor cell survival following transplantation. This is partly 
      attributed to insufficient resistance of transplanted stem cells to oxidative and 
      inflammatory stresses at the injured sites. In the current study, we demonstrated 
      the pivotal role of antioxidant levels in human umbilical cord mesenchymal stem 
      cells (hUCMSCs) dynamic in vitro anti-stress abilities against lipopolysaccharide 
      (LPS)/H2O2 intoxication and in vivo therapeutic efficacy in a murine acute liver 
      failure model induced by D-galactosamine/LPS (Gal/LPS) by either reducing the 
      antioxidant levels with diethyl maleate (DEM) or increasing antioxidant levels 
      with edaravone. Both the anti- and pro-oxidant treatments dramatically influenced 
      the survival, apoptosis, and reactive oxygen species (ROS) production of hUCMSCs 
      through the MAPK-PKC-Nrf2 pathway in vitro. When compared with untreated and 
      DEM-treated cells, edaravone-treated hUCMSCs rescued NOD/SCID mice from 
      Gal/LPS-induced death, significantly improved hepatic functions and promoted host 
      liver regeneration. These effects were probably from increased stem cell homing, 
      promoted proliferation, decreased apoptosis and enhanced secretion of hepatocyte 
      growth factor (HGF) under hepatic stress environment. In conclusion, elevating 
      levels of antioxidants in hUCMSCs with edaravone can significantly influence 
      their hepatic tissue repair capacity.
FAU - Zeng, Wen
AU  - Zeng W
AD  - State key Discipline of Infectious Diseases, Shenzhen Third People's Hospital, 
      Shenzhen, China.
AD  - Laboratory for Gene and Cell Therapy, Shenzhen Institute of Advanced Technology, 
      Chinese Academy of Sciences, Shenzhen, China.
FAU - Xiao, Jia
AU  - Xiao J
AD  - State key Discipline of Infectious Diseases, Shenzhen Third People's Hospital, 
      Shenzhen, China.
AD  - Department of Immunobiology, Institute of Tissue Transplantation and Immunology, 
      Jinan University, Guangzhou, China.
AD  - Department of Anatomy, The University of Hong Kong, Hong Kong, China.
FAU - Zheng, Gang
AU  - Zheng G
AD  - Laboratory for Gene and Cell Therapy, Shenzhen Institute of Advanced Technology, 
      Chinese Academy of Sciences, Shenzhen, China.
FAU - Xing, Feiyue
AU  - Xing F
AD  - Department of Immunobiology, Institute of Tissue Transplantation and Immunology, 
      Jinan University, Guangzhou, China.
FAU - Tipoe, George L
AU  - Tipoe GL
AD  - Department of Anatomy, The University of Hong Kong, Hong Kong, China.
FAU - Wang, Xiaogang
AU  - Wang X
AD  - Department of Immunobiology, Institute of Tissue Transplantation and Immunology, 
      Jinan University, Guangzhou, China.
FAU - He, Chengyi
AU  - He C
AD  - Laboratory for Gene and Cell Therapy, Shenzhen Institute of Advanced Technology, 
      Chinese Academy of Sciences, Shenzhen, China.
FAU - Chen, Zhi-Ying
AU  - Chen ZY
AD  - Laboratory for Gene and Cell Therapy, Shenzhen Institute of Advanced Technology, 
      Chinese Academy of Sciences, Shenzhen, China.
FAU - Liu, Yingxia
AU  - Liu Y
AD  - State key Discipline of Infectious Diseases, Shenzhen Third People's Hospital, 
      Shenzhen, China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20150609
PL  - England
TA  - Sci Rep
JT  - Scientific reports
JID - 101563288
RN  - 0 (Antioxidants)
SB  - IM
MH  - Antioxidants/pharmacology/*therapeutic use
MH  - Humans
MH  - Liver Failure, Acute/*drug therapy
MH  - Mesenchymal Stem Cells/cytology/*drug effects
MH  - Models, Biological
MH  - *Stress, Physiological
PMC - PMC4460871
COIS- The authors declare no competing financial interests.
EDAT- 2015/06/10 06:00
MHDA- 2016/03/29 06:00
PMCR- 2015/06/09
CRDT- 2015/06/10 06:00
PHST- 2015/01/11 00:00 [received]
PHST- 2015/05/12 00:00 [accepted]
PHST- 2015/06/10 06:00 [entrez]
PHST- 2015/06/10 06:00 [pubmed]
PHST- 2016/03/29 06:00 [medline]
PHST- 2015/06/09 00:00 [pmc-release]
AID - srep11100 [pii]
AID - 10.1038/srep11100 [doi]
PST - epublish
SO  - Sci Rep. 2015 Jun 9;5:11100. doi: 10.1038/srep11100.