Conditioned Medium from Human Amnion-Derived Mesenchymal Stem Cells Regulates Activation of Primary Hepatic Stellate Cells
Mesenchymal stem cells (MSCs), or multipotent mesenchymal stromal cells, are present in almost all organs and tissues, including the amnion. Human amnion-derived mesenchymal stem cell (hAMSC) transplantation has been reported to ameliorate liver fibrosis in animal models. However, the mechanism for...
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Wiley
2018-01-01
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| Series: | Stem Cells International |
| Online Access: | http://dx.doi.org/10.1155/2018/4898152 |
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| author | Qingjie Fu Shunsuke Ohnishi Naoya Sakamoto |
| author_facet | Qingjie Fu Shunsuke Ohnishi Naoya Sakamoto |
| author_sort | Qingjie Fu |
| collection | DOAJ |
| description | Mesenchymal stem cells (MSCs), or multipotent mesenchymal stromal cells, are present in almost all organs and tissues, including the amnion. Human amnion-derived mesenchymal stem cell (hAMSC) transplantation has been reported to ameliorate liver fibrosis in animal models. However, the mechanism for the prevention of liver fibrosis is poorly understood. In this study, we investigated the effects, and underlying mechanisms, of a conditioned medium obtained from hAMSC cultures (hAMSC-CM) on a primary culture of rat hepatic stellate cells (HSCs). We observed that in routine culture, hAMSC-CM in HSCs significantly inhibited the expression of alpha-smooth muscle actin (α-SMA), an activation marker of HSCs, and the production of collagen type 1 (COL1), a dominant component of the extracellular matrix (ECM) in the culture medium. In addition, hAMSC-CM upregulated the expression of ECM degradation-related genes, such as metalloproteinase- (Mmp-) 2, Mmp-9, Mmp-13, and tissue inhibitor of metalloproteinase- (Timp-) 1; however, it did not affect the expression of collagen type 1α1 (Col1a1). These regulatory effects on HSCs were concentration-dependent. A cell proliferation assay indicated that hAMSC-CM significantly suppressed HSC proliferation and downregulated the expression of cyclin B (Ccnb), a proliferation-related gene. Transforming growth factor-beta (TGF-β) treatment further activated HSCs and hAMSC-CM significantly inhibited the upregulation of α-Sma and Col1a1 induced by TGF-β. These findings demonstrated that hAMSC-CM can modulate HSC function via secretory factors and provide a plausible explanation for the protective role of hAMSCs in liver fibrosis. |
| format | Article |
| id | doaj-art-509ee32c04cc446dbe467b5eb465c10b |
| institution | Kabale University |
| issn | 1687-966X 1687-9678 |
| language | English |
| publishDate | 2018-01-01 |
| publisher | Wiley |
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| series | Stem Cells International |
| spelling | doaj-art-509ee32c04cc446dbe467b5eb465c10b2025-02-03T05:53:58ZengWileyStem Cells International1687-966X1687-96782018-01-01201810.1155/2018/48981524898152Conditioned Medium from Human Amnion-Derived Mesenchymal Stem Cells Regulates Activation of Primary Hepatic Stellate CellsQingjie Fu0Shunsuke Ohnishi1Naoya Sakamoto2Department of Gastroenterology and Hepatology, Hokkaido University Graduate School of Medicine, Sapporo, JapanDepartment of Gastroenterology and Hepatology, Hokkaido University Graduate School of Medicine, Sapporo, JapanDepartment of Gastroenterology and Hepatology, Hokkaido University Graduate School of Medicine, Sapporo, JapanMesenchymal stem cells (MSCs), or multipotent mesenchymal stromal cells, are present in almost all organs and tissues, including the amnion. Human amnion-derived mesenchymal stem cell (hAMSC) transplantation has been reported to ameliorate liver fibrosis in animal models. However, the mechanism for the prevention of liver fibrosis is poorly understood. In this study, we investigated the effects, and underlying mechanisms, of a conditioned medium obtained from hAMSC cultures (hAMSC-CM) on a primary culture of rat hepatic stellate cells (HSCs). We observed that in routine culture, hAMSC-CM in HSCs significantly inhibited the expression of alpha-smooth muscle actin (α-SMA), an activation marker of HSCs, and the production of collagen type 1 (COL1), a dominant component of the extracellular matrix (ECM) in the culture medium. In addition, hAMSC-CM upregulated the expression of ECM degradation-related genes, such as metalloproteinase- (Mmp-) 2, Mmp-9, Mmp-13, and tissue inhibitor of metalloproteinase- (Timp-) 1; however, it did not affect the expression of collagen type 1α1 (Col1a1). These regulatory effects on HSCs were concentration-dependent. A cell proliferation assay indicated that hAMSC-CM significantly suppressed HSC proliferation and downregulated the expression of cyclin B (Ccnb), a proliferation-related gene. Transforming growth factor-beta (TGF-β) treatment further activated HSCs and hAMSC-CM significantly inhibited the upregulation of α-Sma and Col1a1 induced by TGF-β. These findings demonstrated that hAMSC-CM can modulate HSC function via secretory factors and provide a plausible explanation for the protective role of hAMSCs in liver fibrosis.http://dx.doi.org/10.1155/2018/4898152 |
| spellingShingle | Qingjie Fu Shunsuke Ohnishi Naoya Sakamoto Conditioned Medium from Human Amnion-Derived Mesenchymal Stem Cells Regulates Activation of Primary Hepatic Stellate Cells Stem Cells International |
| title | Conditioned Medium from Human Amnion-Derived Mesenchymal Stem Cells Regulates Activation of Primary Hepatic Stellate Cells |
| title_full | Conditioned Medium from Human Amnion-Derived Mesenchymal Stem Cells Regulates Activation of Primary Hepatic Stellate Cells |
| title_fullStr | Conditioned Medium from Human Amnion-Derived Mesenchymal Stem Cells Regulates Activation of Primary Hepatic Stellate Cells |
| title_full_unstemmed | Conditioned Medium from Human Amnion-Derived Mesenchymal Stem Cells Regulates Activation of Primary Hepatic Stellate Cells |
| title_short | Conditioned Medium from Human Amnion-Derived Mesenchymal Stem Cells Regulates Activation of Primary Hepatic Stellate Cells |
| title_sort | conditioned medium from human amnion derived mesenchymal stem cells regulates activation of primary hepatic stellate cells |
| url | http://dx.doi.org/10.1155/2018/4898152 |
| work_keys_str_mv | AT qingjiefu conditionedmediumfromhumanamnionderivedmesenchymalstemcellsregulatesactivationofprimaryhepaticstellatecells AT shunsukeohnishi conditionedmediumfromhumanamnionderivedmesenchymalstemcellsregulatesactivationofprimaryhepaticstellatecells AT naoyasakamoto conditionedmediumfromhumanamnionderivedmesenchymalstemcellsregulatesactivationofprimaryhepaticstellatecells |