title: Epigenetic Alterations of IL-6/STAT3 Signaling by Placental Stem Cells Promote Hepatic Regeneration in a Rat Model with CCl4-induced Liver Injury.
abstract: BACKGROUND
  Human chorionic plate-derived mesenchymal stem cells (CP-MSCs) isolated from the placenta have been reported to demonstrate therapeutic effects in animal models of liver injury; however, the underlying epigenetic mechanism of this effect has not been elucidated. Thus, we investigated whether CP-MSCs influence epigenetic processes during regeneration of the injured liver.
  
  
  METHODS
  CP-MSCs were engrafted into a carbon tetrachloride (CCl4)-injured rat model through direct transplantation into the liver (DTX), intrasplenic transplantation (STX), and intravenous transplantation via the tail vein (TTX). Non-transplanted (NTX) rats were maintained as sham controls. Liver tissues were analyzed after transplantation using immunohistochemistry, western blot analysis, and quantitative methylation-specific polymerase chain reaction. Proliferation and human interleukin-6 (hIL-6) enzyme-linked immunosorbent assays were performed using CCl4-treated hepatic cells that were co-cultured with CP-MSCs.
  
  
  RESULTS
  The Ki67 labeling index, cell cyclins, albumin, IL-6, and gp130 levels were elevated in the CP-MSC transplantation groups. The concentration of hIL-6 in supernatants and the proliferation of CCl4-treated rat hepatic cells were enhanced by co-culturing with CP-MSCs (p<0.05), while the methylation of IL-6/IL-6R and STAT3 by CP-MSC transplantation decreased.
  
  
  CONCLUSIONS
  These results suggest that administration of CP-MSCs promotes IL-6/STAT3 signaling by decreasing the methylation of the IL-6/SATA3 promoters and thus inducing the proliferation of hepatic cells in a CCl4-injured liver rat model. These data advance our understanding of the therapeutic mechanisms in injured livers, and can facilitate the development of cell-based therapies using placenta-derived stem cells.
authors.affiliation: Department of Biomedical Science, CHA University, Seongnam, Korea ; Department of Nanobiomedical Science, Dankook University, Cheonan, Korea.
authors.forename: Jieun
authors.initials: J
authors.lastname: Jung
authors.affiliation: Institute of Human Genetics, Department of Anatomy, Korea University College of Medicine, Seoul, Korea.
authors.forename: Ji Wook
authors.initials: JW
authors.lastname: Moon
authors.affiliation: Department of Biomedical Science, CHA University, Seongnam, Korea.
authors.forename: Jong-Ho
authors.initials: JH
authors.lastname: Choi
authors.affiliation: Institute of Human Genetics, Department of Anatomy, Korea University College of Medicine, Seoul, Korea.
authors.forename: Yong Woo
authors.initials: YW
authors.lastname: Lee
authors.affiliation: Institute of Human Genetics, Department of Anatomy, Korea University College of Medicine, Seoul, Korea.
authors.forename: Sun-Hwa
authors.initials: SH
authors.lastname: Park
authors.affiliation: Department of Biomedical Science, CHA University, Seongnam, Korea.
authors.forename: Gi Jin
authors.initials: GJ
authors.lastname: Kim
keywords: DNA methylation; IL-6 signaling; Liver regeneration; Placenta stem cells; Transplantation routes