title: Therapeutic potentials occurring during the early differentiation process of mesenchymal stem cells in a rats model with thioacetamide-induced liver fibrosis.
abstract: OBJECTIVE
  Mesenchymal stem cells (MSCs) have the capacity to differentiate into hepatocytes, The purpose of this study is to investigate the MSCs' differentiation process and therapeutic potentials by comparing isolated MSCs with HGF-treated MSCs in rat's model with thiacetamide (TAA)-induced cirrhosis.
  
  
  METHODS
  Male Sprague-Dawley (SD) rats, weighing 100-150 g were used in this study. To induce liver fibrosis, recipient rats were taken with 0.04% thioacetamide (TAA) in the drinking water (400 mg TAA/L) for 8 weeks. The rats underlying liver cirrhosis were divided into 3 groups according to the transplanted materials, compared to normal saline as control (I) and isolated MSCs (II) HGF-treated MSCs.
  
  
  RESULTS
  Severe hepatic fibrosis and hepatocyte destruction were detected in the control group. Less hepatic cirrhosis and collagen formation, more hepatocyte regeneration and glycogen storage were detected in isolated MSCs compared to HGF-treated MSCs group, Distribution of red autofluorescence is mainly localized near the sinusoids in isolated MSCs, scattered away the sinusoids in HGF-treated MSCs group. MSCs transdifferentiated into CK-19 postive Oval cells and then to albulmin-producing hepatocytes, HGF treated MSCs differentiated into hepatocyte without the intermediate oval cells phase. HGF treated MSCs became the CK18-positive, MSCs became CD 90-positive.
  
  
  CONCLUSIONS
  Significant hepatocyte differentiation occurred in not HGF-treated MSCs but isolated MSCs group unexpectedly. These results suggest that the beneficial effect of MSCs on in rat's model with TAA-induced cirrhosis may occur during early differentiation course of MSCs. Mature hepatocyte itself has a little effect on the accelerated differentiation and functional capacity of hepatic lineage cell-line.
authors.affiliation: Department of Surgery, Gachon University Gil Hospital, Incheon, Korea.
authors.forename: Sang-Tae
authors.initials: ST
authors.lastname: Choi
authors.affiliation: Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
authors.forename: Shin
authors.initials: S
authors.lastname: Hwang
authors.affiliation: Department of Anatomy and Cell Biology, University of Ulsan College of Medicine, Seoul, Korea.
authors.forename: Hea-Nam
authors.initials: HN
authors.lastname: Hong
authors.affiliation: Department of Anatomy and Cell Biology, University of Ulsan College of Medicine, Seoul, Korea.
authors.forename: You-Jin
authors.initials: YJ
authors.lastname: Won
authors.affiliation: Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
authors.forename: Chul-Soo
authors.initials: CS
authors.lastname: Ahn
authors.affiliation: Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
authors.forename: Tae-Yong
authors.initials: TY
authors.lastname: Ha
authors.affiliation: Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
authors.forename: Gi-Won
authors.initials: GW
authors.lastname: Song
authors.affiliation: Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
authors.forename: Dong-Hwan
authors.initials: DH
authors.lastname: Jung
authors.affiliation: Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
authors.forename: Gil-Chun
authors.initials: GC
authors.lastname: Park
authors.affiliation: Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
authors.forename: Sung-Gyu
authors.initials: SG
authors.lastname: Lee
keywords: Differentiation; Hepatocyte; Liver cirrhosis; Mesenchymal stem cell; Rat model; Thioacetamide