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.
| Original language | English |
|---|---|
| Pages (from-to) | 79-89 |
| Number of pages | 11 |
| Journal | International Journal of Stem Cells |
| Volume | 8 |
| Issue number | 1 |
| DOIs | |
| Publication status | Published - 2015 Jan 1 |
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Keywords
- DNA methylation
- IL-6 signaling
- Liver regeneration
- Placenta stem cells
- Transplantation routes
ASJC Scopus subject areas
- Developmental Biology
- Cell Biology
Cite this
Epigenetic alterations of IL-6/STAT3 signaling by placental stem cells promote hepatic regeneration in a rat model with CCl4-induced liver injury. / Jung, Jieun; Moon, Ji Wook; Choi, Jong Ho; Lee, Yong Woo; Park, Sun-Hwa; Kim, Gi Jin.
In: International Journal of Stem Cells, Vol. 8, No. 1, 01.01.2015, p. 79-89.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Epigenetic alterations of IL-6/STAT3 signaling by placental stem cells promote hepatic regeneration in a rat model with CCl4-induced liver injury
AU - Jung, Jieun
AU - Moon, Ji Wook
AU - Choi, Jong Ho
AU - Lee, Yong Woo
AU - Park, Sun-Hwa
AU - Kim, Gi Jin
PY - 2015/1/1
Y1 - 2015/1/1
N2 - 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.
AB - 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.
KW - DNA methylation
KW - IL-6 signaling
KW - Liver regeneration
KW - Placenta stem cells
KW - Transplantation routes
UR - http://www.scopus.com/inward/record.url?scp=84930396802&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84930396802&partnerID=8YFLogxK
U2 - 10.15283/ijsc.2015.8.1.79
DO - 10.15283/ijsc.2015.8.1.79
M3 - Article
AN - SCOPUS:84930396802
VL - 8
SP - 79
EP - 89
JO - International Journal of Stem Cells
JF - International Journal of Stem Cells
SN - 2005-3606
IS - 1
ER -