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2015 ; 8
(1
): 79-89
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English Wikipedia
Epigenetic Alterations of IL-6/STAT3 Signaling by Placental Stem Cells Promote
Hepatic Regeneration in a Rat Model with CCl4-induced Liver Injury
#MMPMID26019757
Jung J
; Moon JW
; Choi JH
; Lee YW
; Park SH
; Kim GJ
Int J Stem Cells
2015[May]; 8
(1
): 79-89
PMID26019757
show ga
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.