Epigenetic Alterations of IL-6/STAT3 Signaling by Placental Stem Cells Promote Hepatic Regeneration in a Rat Model with CCl4-induced Liver Injury.
10.15283/ijsc.2015.8.1.79
- Author:
Jieun JUNG
1
;
Ji Wook MOON
;
Jong Ho CHOI
;
Yong Woo LEE
;
Sun Hwa PARK
;
Gi Jin KIM
Author Information
1. Department of Biomedical Science, CHA University, Seongnam, Korea. gjkim@cha.ac.kr
- Publication Type:Original Article
- Keywords:
Placenta stem cells;
Liver regeneration;
Transplantation routes;
IL-6 signaling;
DNA methylation
- MeSH:
Animals;
Blotting, Western;
Carbon Tetrachloride;
Chorion;
Cyclins;
DNA Methylation;
Enzyme-Linked Immunosorbent Assay;
Epigenesis, Genetic;
Epigenomics*;
Hepatocytes;
Humans;
Immunohistochemistry;
Interleukin-6;
Liver Regeneration;
Liver*;
Mesenchymal Stromal Cells;
Methylation;
Models, Animal*;
Placenta;
Polymerase Chain Reaction;
Rats;
Regeneration*;
Stem Cells*;
Veins
- From:International Journal of Stem Cells
2015;8(1):79-89
- CountryRepublic of Korea
- Language:English
-
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. CONCLUSION: 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.
