PMID- 25108650
OWN - NLM
STAT- MEDLINE
DCOM- 20150416
LR  - 20220408
IS  - 1477-2566 (Electronic)
IS  - 1465-3249 (Linking)
VI  - 16
IP  - 9
DP  - 2014 Sep
TI  - Human umbilical cord mesenchymal stromal cells rescue mice from 
      acetaminophen-induced acute liver failure.
PG  - 1207-19
LID - S1465-3249(14)00636-7 [pii]
LID - 10.1016/j.jcyt.2014.05.018 [doi]
AB  - BACKGROUND AIMS: 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-alpha, 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.
CI  - Copyright (c) 2014 International Society for Cellular Therapy. Published by 
      Elsevier Inc. All rights reserved.
FAU - Liu, Zongcai
AU  - Liu Z
AD  - Shenzhen Beike Cell Engineering Research Institute, Yuanxing Science and 
      Technology Building, Nanshan, Shenzhen, PR China.
FAU - Meng, Fanwei
AU  - Meng F
AD  - Shenzhen Beike Cell Engineering Research Institute, Yuanxing Science and 
      Technology Building, Nanshan, Shenzhen, PR China.
FAU - Li, Chan
AU  - Li C
AD  - Shenzhen Beike Cell Engineering Research Institute, Yuanxing Science and 
      Technology Building, Nanshan, Shenzhen, PR China.
FAU - Zhou, Xin
AU  - Zhou X
AD  - Shenzhen Beike Cell Engineering Research Institute, Yuanxing Science and 
      Technology Building, Nanshan, Shenzhen, PR China.
FAU - Zeng, Xiaoping
AU  - Zeng X
AD  - Shenzhen Beike Cell Engineering Research Institute, Yuanxing Science and 
      Technology Building, Nanshan, Shenzhen, PR China.
FAU - He, Yixin
AU  - He Y
AD  - Shenzhen Beike Cell Engineering Research Institute, Yuanxing Science and 
      Technology Building, Nanshan, Shenzhen, PR China.
FAU - Mrsny, Randall J
AU  - Mrsny RJ
AD  - GMR Epigenetics, Palo Alto, California, USA; Department of Pharmacy & 
      Pharmacology, University of Bath, Bath, England.
FAU - Liu, Muyun
AU  - Liu M
AD  - Shenzhen Beike Cell Engineering Research Institute, Yuanxing Science and 
      Technology Building, Nanshan, Shenzhen, PR China.
FAU - Hu, Xiang
AU  - Hu X
AD  - Shenzhen Beike Cell Engineering Research Institute, Yuanxing Science and 
      Technology Building, Nanshan, Shenzhen, PR China.
FAU - Hu, Ji-Fan
AU  - Hu JF
AD  - 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.
FAU - Li, Tao
AU  - Li T
AD  - Shenzhen Beike Cell Engineering Research Institute, Yuanxing Science and 
      Technology Building, Nanshan, Shenzhen, PR China. Electronic address: 
      litao@beike.cc.
LA  - eng
GR  - 1R43 CA103553-01/CA/NCI NIH HHS/United States
GR  - R01 DK056754-11A1/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PL  - England
TA  - Cytotherapy
JT  - Cytotherapy
JID - 100895309
RN  - 362O9ITL9D (Acetaminophen)
RN  - EC 2.6.1.1 (Aspartate Aminotransferases)
RN  - EC 2.6.1.2 (Alanine Transaminase)
RN  - RFM9X3LJ49 (Bilirubin)
SB  - IM
MH  - Acetaminophen/administration & dosage/*toxicity
MH  - Administration, Intravenous
MH  - Alanine Transaminase/blood
MH  - Animals
MH  - Aspartate Aminotransferases/blood
MH  - Bilirubin/blood
MH  - Cell Differentiation
MH  - Cells, Cultured
MH  - Disease Models, Animal
MH  - Humans
MH  - Liver/*metabolism/pathology
MH  - Liver Failure, Acute/chemically induced/*therapy
MH  - Male
MH  - *Mesenchymal Stem Cell Transplantation
MH  - Mesenchymal Stem Cells/*physiology
MH  - Mice, Inbred BALB C
MH  - Umbilical Cord/cytology
OTO - NOTNLM
OT  - acute liver failure
OT  - anti-inflammation
OT  - antioxidants
OT  - apoptosis
OT  - hepatic regeneration
OT  - umbilical cord mesenchymal stromal cells
EDAT- 2014/08/12 06:00
MHDA- 2015/04/17 06:00
CRDT- 2014/08/11 06:00
PHST- 2013/10/21 00:00 [received]
PHST- 2014/04/25 00:00 [revised]
PHST- 2014/05/20 00:00 [accepted]
PHST- 2014/08/11 06:00 [entrez]
PHST- 2014/08/12 06:00 [pubmed]
PHST- 2015/04/17 06:00 [medline]
AID - S1465-3249(14)00636-7 [pii]
AID - 10.1016/j.jcyt.2014.05.018 [doi]
PST - ppublish
SO  - Cytotherapy. 2014 Sep;16(9):1207-19. doi: 10.1016/j.jcyt.2014.05.018.