Epigenetic Alterations of IL-6/STAT3 Signaling by Placental Stem Cells Promote Hepatic Regeneration in a Rat Model with CCl4-induced Liver Injury
International Journal of Stem Cells
; : 79-89, 2015.
Article
in English
| WPRIM (Western Pacific)
| ID: wpr-171257
Responsible library:
WPRO
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.
Full text:
Available
Database:
WPRIM (Western Pacific)
Main subject:
Placenta
/
Regeneration
/
Stem Cells
/
Veins
/
Enzyme-Linked Immunosorbent Assay
/
Carbon Tetrachloride
/
Immunohistochemistry
/
Blotting, Western
/
Polymerase Chain Reaction
/
Chorion
Type of study:
Prognostic study
Limits:
Animals
/
Humans
Language:
English
Journal:
International Journal of Stem Cells
Year:
2015
Document type:
Article