title: Embryonic hepatocyte transplantation for hepatic cirrhosis: efficacy and mechanism of action.
abstract: OBJECTIVE
  To investigate the efficacy and mechanism of action of allogeneic embryonic hepatocyte transplantation for the treatment of hepatic cirrhosis.
  
  
  METHODS
  Rat embryonic hepatocytes were characterized by examining cell markers. Wistar rats with CCl(4)-induced cirrhosis were randomly divided into two groups: a model group receiving continuous CCl(4), and a cell transplantation group receiving continuous CCl(4) and transplanted with embryonic fluorescent-labeled hepatocytes. In addition, a normal control group was composed of healthy rats. All rats were sacrificed after 2 wk following the initiation of the cell transplant. Ultrasound, pathological analyses and serum biochemical tests were used to evaluate the efficacy of embryonic hepatocyte transplantation. To analyze the recovery status of cirrhotic hepatocytes and the signaling pathways influenced by embryonic hepatocyte transplantation, real-time polymerase chain reaction was performed to examine the mRNA expression of stellate activation-associated protein (STAP), c-myb, α smooth muscle actin (α-SMA) and endothelin-1 (ET-1). Western blotting and immunohistochemistry were employed to detect α-SMA and ET-1 protein expression in hepatic tissues.
  
  
  RESULTS
  Gross morphological, ultrasound and histopathological examinations, serum biochemical tests and radioimmunoassays demonstrated that hepatic cirrhosis was successfully established in the Wistar rats. Stem cell factor receptor (c-kit), hepatocyte growth factor receptor (c-Met), Nestin, α fetal protein, albumin and cytokeratin19 markers were observed in the rat embryonic hepatocytes. Following embryonic hepatocyte transplantation, there was a significant reversal in the gross appearance, ultrasound findings, histopathological properties, and serum biochemical parameters of the rat liver. In addition, after the activation of hepatic stellate cells and STAP signaling, α-SMA, c-myb and ET-1 mRNA levels became significantly lower than in the untreated cirrhotic group (P < 0.05). These levels, however, were not statistically different from those of the normal healthy group. Immunohistochemical staining and Western blot analyses revealed that α-SMA and ET-1 protein expression levels in the transplantation group were significantly lower than in the untreated cirrhotic group, but being not statistically different from the normal group.
  
  
  CONCLUSIONS
  Transplantation of embryonic hepatocytes in rats has therapeutic effects on cirrhosis. The described treatment may significantly reduce the expression of STAP and ET-1.
authors.affiliation: Laboratory of Reproductive Biology, Department of Histology and Embryology, School of Basic Medical Sciences, Capital Medical University, Beijing 100069, China.
authors.forename: Wen-Ting
authors.initials: WT
authors.lastname: Bin
authors.forename: Li-Mei
authors.initials: LM
authors.lastname: Ma
authors.forename: Qing
authors.initials: Q
authors.lastname: Xu
authors.forename: Xiao-Lin
authors.initials: XL
authors.lastname: Shi
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D002251:Carbon Tetrachloride / Q000633:toxicity; D000078842:Cytoglobin; D004622:Embryo, Mammalian / Q000166:cytology*; D019332:Endothelin-1 / Q000378:metabolism; D005260:Female; D022781:Hepatocytes / Q000378:metabolism / Q000637:transplantation*; D008099:Liver / Q000166:cytology / Q000378:metabolism / Q000473:pathology; D008106:Liver Cirrhosis, Experimental / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology / Q000601:surgery*; D008297:Male; D010544:Peroxidases / Q000378:metabolism; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction / Q000502:physiology
chemical_list: D015415:Biomarkers; C000627268:Cygb protein, rat; D000078842:Cytoglobin; D019332:Endothelin-1; D002251:Carbon Tetrachloride; D010544:Peroxidases