Human hepatocyte growth factor (hHGF)-modified hepatic oval cells improve liver transplant survival

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 simultaneousl...

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Bibliographic Details
Published in:PloS one 2012-09, Vol.7 (9), p.e44805-e44805
Main Authors: Li, Zhu, Chen, Juan, Li, Li, Ran, Jiang-Hua, Li, Xue-Hua, Liu, Zhi-Heng, Liu, Gui-Jie, Gao, Yan-Chao, Zhang, Xue-Li, Sun, Hiu-Dong
Format: Article
Language:English
Subjects:
Allografts
Analysis
Animal tissues
Animals
Apoptosis
Bile
Bile ducts
Biology
Care and treatment
Cell Proliferation
Cell survival
Cytokines - metabolism
Epithelial cells
Gene expression
Genetic aspects
Graft rejection
Graft Rejection - prevention & control
Graft Survival
Grafting
Growth factors
Hepatectomy
Hepatocyte growth factor
Hepatocyte Growth Factor - metabolism
Hepatocytes
HGF gene
Hospitals
Humans
Hybridization
Immune response
Immunosuppression
Interferon
Interleukin 10
Interleukin 2
Liver
Liver - cytology
Liver - metabolism
Liver - physiology
Liver diseases
Liver Transplantation
Liver transplants
Male
Medicine
Patient outcomes
Physiological aspects
Rats
Rejection
Rodents
Stem Cell Transplantation
Stem cells
Stem Cells - metabolism
Surgery
Survival
Survival Rate
Transfection
Transforming growth factor-b1
Transplantation
Transplants & implants
Tumor necrosis factor-α
γ-Interferon
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Summary: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
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0044805