title: Therapeutic potential of amniotic-fluid-derived stem cells on liver fibrosis model in mice.
abstract: OBJECTIVE
  Liver fibrosis results from the wound healing response to chronic liver damage. Advanced liver fibrosis results in cirrhosis and liver failure, and liver transplantation is often the only option for effective therapy; however, the shortage of available donor livers limits this treatment. Thus, new therapies for advanced liver fibrosis are essential.
  
  
  METHODS
  Amniotic fluid contains an abundance of stem cells, which are derived from all three germ layers of the developing fetus. These cells do not induce teratomas in vivo and do not pose any ethical concerns. To generate liver fibrosis models, male ICR mice were treated with CCl4 via oral gavage for 4 weeks, and the serum levels of glutamate oxaloacetate transaminase, glutamate pyruvate transaminase, and albumin were higher than in the control group following chemical induction. To assess the potential of amniotic-fluid-derived stem cells (mAFSCs) to ameliorate liver fibrosis in vivo, mAFSCs were isolated from amniotic fluid of 13.5-day-old transgenic mice, which globally express the fluorescent protein, enhanced green fluorescent protein (EGFP), for tracing purposes (EGFP-mAFSCs). Single cells were injected via the mesentery (1 × 10(6) cells/mouse) of transplanted mice with liver fibrosis.
  
  
  RESULTS
  Four weeks after EGFP-mAFSC transplantation, the serum glutamate oxaloacetate transaminase, glutamate pyruvate transaminase, and albumin levels of recipient mice in the EGFP-mAFSC-injected group were significantly decreased when compared with mice in the saline-injected group. Additionally, fibrotic tissues were evaluated using Masson's trichrome staining 4 weeks after cell transplantation. Shrinkage of the fibrotic area was observed in the EGFP-mAFSC-injected group. The tissue-repair effects were also confirmed by hydroxyproline content analysis.
  
  
  CONCLUSIONS
  The possible repair mechanism from our data revealed that EGFP-mAFSCs may fuse with the recipient liver cells. Overall, EGFP-mAFSCs can ameliorate liver fibrosis in mice, thus providing insight into the future development of regenerative medicine.
authors.affiliation: Institute of Biotechnology, National Taiwan University, Taipei, Taiwan.
authors.forename: Shao-Yu
authors.initials: SY
authors.lastname: Peng
authors.affiliation: Institute of Biotechnology, National Taiwan University, Taipei, Taiwan.
authors.forename: Chih-Jen
authors.initials: CJ
authors.lastname: Chou
authors.affiliation: Department of Obstetrics and Gynaecology, Chang Gung Memorial Hospital at Linkou and Chang Gung University, College of Medicine, Taoyuan, Taiwan.
authors.forename: Po-Jen
authors.initials: PJ
authors.lastname: Cheng
authors.affiliation: Department of Animal Science and Technology, National Taiwan University, Taipei, Taiwan.
authors.forename: I-Chen
authors.initials: IC
authors.lastname: Ko
authors.affiliation: Department of Animal Science and Technology, National Taiwan University, Taipei, Taiwan.
authors.forename: Yi-Jung
authors.initials: YJ
authors.lastname: Kao
authors.affiliation: Institute of Biotechnology, National Taiwan University, Taipei, Taiwan; Department of Surgery, Hualien Armed Forces General Hospital, Hualien, Taiwan.
authors.forename: Yu-Hsu
authors.initials: YH
authors.lastname: Chen
authors.affiliation: Department of Animal Science and Technology, National Taiwan University, Taipei, Taiwan; Department of Animal Science and Biotechnology, Tunghai University, Taichung, Taiwan.
authors.forename: Winston Teng-Kui
authors.initials: WT
authors.lastname: Cheng
authors.affiliation: Department of Obstetrics and Gynaecology, Chang Gung Memorial Hospital at Linkou and Chang Gung University, College of Medicine, Taoyuan, Taiwan; Research Center for Developmental Biology and Regenerative Medicine, National Taiwan University, Taipei, Taiwan; Prenatal Cell and Gene Therapy Group, Institute for Women's Health, University College London, London, UK. Electronic address: dr.shaw@me.com.
authors.forename: S W Steven
authors.initials: SW
authors.lastname: Shaw
authors.affiliation: Institute of Biotechnology, National Taiwan University, Taipei, Taiwan; Department of Animal Science and Technology, National Taiwan University, Taipei, Taiwan. Electronic address: scw01@ntu.edu.tw.
authors.forename: Shinn-Chih
authors.initials: SC
authors.lastname: Wu
mesh_terms: D000410:Alanine Transaminase / Q000097:blood; D000653:Amniotic Fluid / Q000166:cytology*; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D002251:Carbon Tetrachloride; D004195:Disease Models, Animal; D053686:Fetal Stem Cells / Q000637:transplantation*; D006909:Hydroxyproline / Q000032:analysis; D008099:Liver / Q000737:chemistry; D008103:Liver Cirrhosis / Q000097:blood / Q000139:chemically induced / Q000473:pathology / Q000628:therapy*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D012709:Serum Albumin / Q000378:metabolism
chemical_list: D012709:Serum Albumin; D002251:Carbon Tetrachloride; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D006909:Hydroxyproline
keywords: amniotic-fluid-derived stem cells; liver fibrosis; mice; transplantation