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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.
Artigo em Inglês | WPRIM | ID: wpr-171257
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.
Assuntos

Texto completo: DisponíveL Índice: WPRIM (Pacífico Ocidental) Assunto principal: Placenta / Regeneração / Células-Tronco / Veias / Ensaio de Imunoadsorção Enzimática / Tetracloreto de Carbono / Imuno-Histoquímica / Western Blotting / Reação em Cadeia da Polimerase / Córion Tipo de estudo: Estudo prognóstico Limite: Animais / Humanos Idioma: Inglês Revista: International Journal of Stem Cells Ano de publicação: 2015 Tipo de documento: Artigo

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Texto completo: DisponíveL Índice: WPRIM (Pacífico Ocidental) Assunto principal: Placenta / Regeneração / Células-Tronco / Veias / Ensaio de Imunoadsorção Enzimática / Tetracloreto de Carbono / Imuno-Histoquímica / Western Blotting / Reação em Cadeia da Polimerase / Córion Tipo de estudo: Estudo prognóstico Limite: Animais / Humanos Idioma: Inglês Revista: International Journal of Stem Cells Ano de publicação: 2015 Tipo de documento: Artigo