PMID- 23028627
OWN - NLM
STAT- MEDLINE
DCOM- 20130305
LR  - 20240313
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 7
IP  - 9
DP  - 2012
TI  - Human hepatocyte growth factor (hHGF)-modified hepatic oval cells improve liver 
      transplant survival.
PG  - e44805
LID - 10.1371/journal.pone.0044805 [doi]
LID - e44805
AB  - Despite progress in the field of immunosuppression, acute rejection is still a 
      common postoperative complication following liver transplantation. This study 
      aims to investigate the capacity of the human hepatocyte growth factor (hHGF) in 
      modifying hepatic oval cells (HOCs) administered simultaneously with orthotopic 
      liver transplantation as a means of improving graft survival. HOCs were activated 
      and isolated using a modified 2-acetylaminofluorene/partial hepatectomy 
      (2-AAF/PH) model in male Lewis rats. A HOC line stably expressing the HGF gene 
      was established following stable transfection of the pBLAST2-hHGF plasmid. Our 
      results demonstrated that hHGF-modified HOCs could efficiently differentiate into 
      hepatocytes and bile duct epithelial cells in vitro. Administration of HOCs at 
      the time of liver transplantation induced a wider distribution of SRY-positive 
      donor cells in liver tissues. Administration of hHGF-HOC at the time of 
      transplantation remarkably prolonged the median survival time and improved liver 
      function for recipients compared to these parameters in the other treatment 
      groups (P<0.05). Moreover, hHGF-HOC administration at the time of liver 
      transplantation significantly suppressed elevation of interleukin-2 (IL-2), tumor 
      necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma) levels while increasing the 
      production of IL-10 and TGF-beta1 (P<0.05). HOC or hHGF-HOC administration promoted 
      cell proliferation, reduced cell apoptosis, and decreased liver allograft 
      rejection rates. Furthermore, hHGF-modified HOCs more efficiently reduced acute 
      allograft rejection (P<0.05 versus HOC transplantation only). Our results 
      indicate that the combination of hHGF-modified HOCs with liver transplantation 
      decreased host anti-graft immune responses resulting in a reduction of allograft 
      rejection rates and prolonging graft survival in recipient rats. This suggests 
      that HOC-based cell transplantation therapies can be developed as a means of 
      treating severe liver injuries.
FAU - Li, Zhu
AU  - Li Z
AD  - Department of Hepatobiliary Surgery, Liaocheng People's Hospital, Liaocheng, 
      Shandong, China. lllllzhu@126.com
FAU - Chen, Juan
AU  - Chen J
FAU - Li, Li
AU  - Li L
FAU - Ran, Jiang-Hua
AU  - Ran JH
FAU - Li, Xue-Hua
AU  - Li XH
FAU - Liu, Zhi-Heng
AU  - Liu ZH
FAU - Liu, Gui-Jie
AU  - Liu GJ
FAU - Gao, Yan-Chao
AU  - Gao YC
FAU - Zhang, Xue-Li
AU  - Zhang XL
FAU - Sun, Hiu-Dong
AU  - Sun HD
LA  - eng
PT  - Journal Article
DEP - 20120918
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Cytokines)
RN  - 67256-21-7 (Hepatocyte Growth Factor)
SB  - IM
MH  - Animals
MH  - Apoptosis
MH  - Cell Proliferation
MH  - Cytokines/metabolism
MH  - Graft Rejection/prevention & control
MH  - *Graft Survival
MH  - Hepatocyte Growth Factor/*metabolism
MH  - Humans
MH  - Liver/*cytology/metabolism/physiology
MH  - *Liver Transplantation
MH  - Male
MH  - Rats
MH  - *Stem Cell Transplantation
MH  - Stem Cells/*metabolism
MH  - Survival Rate
PMC - PMC3445612
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2012/10/03 06:00
MHDA- 2013/03/06 06:00
PMCR- 2012/09/18
CRDT- 2012/10/03 06:00
PHST- 2012/04/16 00:00 [received]
PHST- 2012/08/14 00:00 [accepted]
PHST- 2012/10/03 06:00 [entrez]
PHST- 2012/10/03 06:00 [pubmed]
PHST- 2013/03/06 06:00 [medline]
PHST- 2012/09/18 00:00 [pmc-release]
AID - PONE-D-12-10749 [pii]
AID - 10.1371/journal.pone.0044805 [doi]
PST - ppublish
SO  - PLoS One. 2012;7(9):e44805. doi: 10.1371/journal.pone.0044805. Epub 2012 Sep 18.