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Mesenchymal stem cells mitigate cirrhosis through BMP7
1Liver Fibrosis Diagnosis and Treatment Center, 302 Hospital of PLA, Beijing, China.
Background/Aims:
Transplantation of mesenchymal stem cells (MSCs) has therapeutic effects on various diseases, while its effect on developing cirrhosis as well as the underlying mechanism remained largely unknown.
Methods:
Twenty C57BL/6 mice were randomly separated into 2 groups of ten each. One group received transplantation of MSCs, while the other group received saline as control. The mice then received intraperitoneal injection of carbon tetrachloride (CCl4) twice per week for 8 weeks to develop cirrhosis. After another 4 weeks, the levels of cirrhosis in these mice were evaluated by liver fibrosis area, portal pressure, sodium balance and excretion. Transcripts of transforming growth factor β 1 (TGFβ1) and bone morphogenic protein 7 (BMP7) in the mouse livers were quantified by RT-qPCR. BMP7-depleted MSCs were prepared and applied in this model, and compared to MSCs.
Results:
Liver fibrosis, portal hypertension and sodium retention that were developed by CCl4, were all significantly alleviated by MSCs transplantation, which decreased TGFβ1 levels and increased BMP7 levels in the injured liver. MSCs were found to express extremely high levels of BMP7. Knockdown of BMP7 in MSCs completely abolished the protective effect of MSCs against CCl4-induced cirrhosis.
Conclusions:
MSCs mitigate cirrhosis through their production of BMP7 against the fibrogenic effect of TGFβ1 in the injured liver.
Insights
Mesenchymal stem cell (MSC) transplantation alleviates carbon tetrachloride-induced liver cirrhosis in mice. This therapeutic effect is mediated by bone morphogenic protein 7 (BMP7), which counteracts the fibrogenic transforming growth factor beta 1 (TGFβ1).
Area of Science:
- Hepatology
- Stem Cell Biology
- Fibrosis Research
Background:
- Mesenchymal stem cells (MSCs) show therapeutic potential across diseases.
- The role and mechanism of MSCs in cirrhosis development and treatment were largely unexplored.
Purpose of the Study:
- To investigate the therapeutic effect of MSCs on developing cirrhosis.
- To elucidate the underlying molecular mechanisms, focusing on TGFβ1 and BMP7.
Main Methods:
- Carbon tetrachloride (CCl4) was used to induce cirrhosis in C57BL/6 mice.
- Mice received MSC transplantation or saline control, followed by evaluation of liver fibrosis, portal pressure, and sodium balance.
- Gene expression of TGFβ1 and BMP7 was quantified; BMP7-depleted MSCs were also tested.
Main Results:
- MSC transplantation significantly alleviated liver fibrosis, portal hypertension, and sodium retention.
- MSCs decreased TGFβ1 and increased BMP7 levels in injured livers.
- BMP7 expression by MSCs was crucial, as BMP7 depletion abolished their protective effects.
Conclusions:
- MSCs mitigate cirrhosis by producing BMP7, which antagonizes the fibrogenic effects of TGFβ1.
- BMP7 is a key mediator of MSCs' protective action against liver fibrosis.
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