Mesenchymal stem cells-conditioned medium reduces liver fibrosis by regulating hepatic stellate cells
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    Abstract:

    Objective: To investigate whether the MSC-conditioned medium(MSC-CM) can protect injured liver and reduce liver fibrosis and its potential mechanisms. Methods: Six-week-old SD rats were allocated into three groups(each group n=8) as follows: model group; treatment group; normal group. The liver fibrosis model was established by intraperitoneal injection of low dose of CCL4(1.5 mL/kg)twice a week for eight weeks. MSCs were grown for 3~5 generation for the preparation of MSC-CM, which was concentrated 25-fold using ultrafiltration. From weeks 5 to 8, MSC-CM was injected every day with a dose of 2 mg/kg by tail vein in the treatment group; at the same time, the other two groups were injected with the same dose of L-DMEM. At the end of the experiment, hepatic stellate cells (HSCs) were isolated by in situ perfusion and density gradient centrifugation, and liver tissue was collected for pathologic analysis. The collagenous fiber was detected by Masson staining, while the expression of alpha-smooth muscle actin(α-SMA) in liver tissues was measured by immunohistochemical staining. To evaluate liver fibrosis, the gene and protein expression of α-SMA, transforming growth factor beta 1(TGF-β1), collagen I , matrix metalloproteinases-2(MMP-2), tissue inhibitor of metalloproteinases-2 (TIMP-2) in HSCs were evaluated by quantitative real-time PCR and Western blot. Results: In liver tissues, histological improvement was observed in hepatic fibrosis after MSC-CM treatment(P<0.01); the expression of α-SMA and collagenous fiber was significantly lower in the treatment group compared to the model group(P<0.05) , but not equal to the normal group. In HSC study, the mRNA expressions of TGF-β1,α-SMA,collagen Ⅰin the treatment group were significantly decreased than those in the model group(P<0.05); and their protein expressions were also lower in the treatment group(P<0.05),and the mRNA expression of MMP-2 increased compared to the model group. Conclusion: Our results showed that MSC-CM has a therapeutic effect on CCL4-induced liver fibrosis. And this process may be related to down-regulaing expression of TGF-β1, inhibiting HSCs activation and promoting collagen degradation.

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郭圆圆,樊圆圆,张永婷,王 瑜,王媛慧,蔡 洁,李 军,章莉莉.间充质干细胞培养上清抑制星状细胞活化治疗肝纤维化的研究[J].南京医科大学学报(自然科学版英文版),2017,(9):1142-1147.

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  • Received:February 27,2017
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  • Online: September 25,2017
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