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Bone marrow-derived mesenchymal stem cells inhibit the proliferation of hepatic stellate cells by inhibiting the transforming growth factor β pathway

Bone marrow-derived mesenchymal stem cells (BM-MSCs) are considered to be a potential therapy for end-stage liver disease. However, the therapeutic mechanism of BM-MSCs remains unclear. The aim of the current study was to investigate the role of paracrine signaling in BM-MSCs in liver cirrhosis in v...

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Autores principales: ZHANG, LI-TING, FANG, XUE-QIN, CHEN, QING-FENG, CHEN, HONG, XIAO, PING, PENG, XUE-BIN, ZHANG, SHENG-XIANG, LI, JUN-FENG, MAO, XIAO-RONG
Formato: Online Artículo Texto
Lenguaje:English
Publicado: D.A. Spandidos 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4626145/
https://www.ncbi.nlm.nih.gov/pubmed/26458849
http://dx.doi.org/10.3892/mmr.2015.4362
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author ZHANG, LI-TING
FANG, XUE-QIN
CHEN, QING-FENG
CHEN, HONG
XIAO, PING
PENG, XUE-BIN
ZHANG, SHENG-XIANG
LI, JUN-FENG
MAO, XIAO-RONG
author_facet ZHANG, LI-TING
FANG, XUE-QIN
CHEN, QING-FENG
CHEN, HONG
XIAO, PING
PENG, XUE-BIN
ZHANG, SHENG-XIANG
LI, JUN-FENG
MAO, XIAO-RONG
author_sort ZHANG, LI-TING
collection PubMed
description Bone marrow-derived mesenchymal stem cells (BM-MSCs) are considered to be a potential therapy for end-stage liver disease. However, the therapeutic mechanism of BM-MSCs remains unclear. The aim of the current study was to investigate the role of paracrine signaling in BM-MSCs in liver cirrhosis in vitro. Human BM-MSCs and hepatic stellate cells (HSCs) were cultured using a vertical double cell co-culture system. Groups were divided into HSCs alone (control group) and the co-culture system of BM-MSCs with HSCs (experimental group). HSC morphology was observed by inverted phase contrast microscopy. The proliferative capacity of HSCs was measured with the MTT assay and flow cytometry. Hoechst staining was performed to examine the apoptosis of HSCs. Transforming growth factor (TGF)-β1 and Smad7 mRNA expression were detected by reverse transcription-quantitative polymerase chain reaction and western blotting. BM-MSCs did not inhibit the proliferation of HSCs at 24 h, however significantly inhibited the proliferation of HSCs at 48 and 72 h. BM-MSCs additionally induced the apoptosis of HSCs at 48 h. The concentration of TGF-β1 in the supernatant at 24 h and 48 h in the co-cultured system was observed to be significantly lower than in the control group (P<0.05). The level of TGF-β1 mRNA in the experimental group at 48 h was significantly lower than the control group, however Smad7 mRNA levels were significantly greater than in the control group. Additionally, TGF-β1 protein levels were significantly lower than in the control group, however levels of Smad7 were greater than the control group. It was concluded that BM-MSCs are able to inhibit the proliferation and promote the apoptosis of HSCs. In addition, the mechanism may be associated with inhibition of the TGF-β1/Smad pathway in HSCs.
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spelling pubmed-46261452016-02-23 Bone marrow-derived mesenchymal stem cells inhibit the proliferation of hepatic stellate cells by inhibiting the transforming growth factor β pathway ZHANG, LI-TING FANG, XUE-QIN CHEN, QING-FENG CHEN, HONG XIAO, PING PENG, XUE-BIN ZHANG, SHENG-XIANG LI, JUN-FENG MAO, XIAO-RONG Mol Med Rep Articles Bone marrow-derived mesenchymal stem cells (BM-MSCs) are considered to be a potential therapy for end-stage liver disease. However, the therapeutic mechanism of BM-MSCs remains unclear. The aim of the current study was to investigate the role of paracrine signaling in BM-MSCs in liver cirrhosis in vitro. Human BM-MSCs and hepatic stellate cells (HSCs) were cultured using a vertical double cell co-culture system. Groups were divided into HSCs alone (control group) and the co-culture system of BM-MSCs with HSCs (experimental group). HSC morphology was observed by inverted phase contrast microscopy. The proliferative capacity of HSCs was measured with the MTT assay and flow cytometry. Hoechst staining was performed to examine the apoptosis of HSCs. Transforming growth factor (TGF)-β1 and Smad7 mRNA expression were detected by reverse transcription-quantitative polymerase chain reaction and western blotting. BM-MSCs did not inhibit the proliferation of HSCs at 24 h, however significantly inhibited the proliferation of HSCs at 48 and 72 h. BM-MSCs additionally induced the apoptosis of HSCs at 48 h. The concentration of TGF-β1 in the supernatant at 24 h and 48 h in the co-cultured system was observed to be significantly lower than in the control group (P<0.05). The level of TGF-β1 mRNA in the experimental group at 48 h was significantly lower than the control group, however Smad7 mRNA levels were significantly greater than in the control group. Additionally, TGF-β1 protein levels were significantly lower than in the control group, however levels of Smad7 were greater than the control group. It was concluded that BM-MSCs are able to inhibit the proliferation and promote the apoptosis of HSCs. In addition, the mechanism may be associated with inhibition of the TGF-β1/Smad pathway in HSCs. D.A. Spandidos 2015-11 2015-09-25 /pmc/articles/PMC4626145/ /pubmed/26458849 http://dx.doi.org/10.3892/mmr.2015.4362 Text en Copyright: © Zhang et al. This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License (https://creativecommons.org/licenses/by-nc-nd/4.0/) , which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.
spellingShingle Articles
ZHANG, LI-TING
FANG, XUE-QIN
CHEN, QING-FENG
CHEN, HONG
XIAO, PING
PENG, XUE-BIN
ZHANG, SHENG-XIANG
LI, JUN-FENG
MAO, XIAO-RONG
Bone marrow-derived mesenchymal stem cells inhibit the proliferation of hepatic stellate cells by inhibiting the transforming growth factor β pathway
title Bone marrow-derived mesenchymal stem cells inhibit the proliferation of hepatic stellate cells by inhibiting the transforming growth factor β pathway
title_full Bone marrow-derived mesenchymal stem cells inhibit the proliferation of hepatic stellate cells by inhibiting the transforming growth factor β pathway
title_fullStr Bone marrow-derived mesenchymal stem cells inhibit the proliferation of hepatic stellate cells by inhibiting the transforming growth factor β pathway
title_full_unstemmed Bone marrow-derived mesenchymal stem cells inhibit the proliferation of hepatic stellate cells by inhibiting the transforming growth factor β pathway
title_short Bone marrow-derived mesenchymal stem cells inhibit the proliferation of hepatic stellate cells by inhibiting the transforming growth factor β pathway
title_sort bone marrow-derived mesenchymal stem cells inhibit the proliferation of hepatic stellate cells by inhibiting the transforming growth factor β pathway
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4626145/
https://www.ncbi.nlm.nih.gov/pubmed/26458849
http://dx.doi.org/10.3892/mmr.2015.4362
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