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丁酸钠预处理增强骨髓间充质干细胞(BM-MSCs)向肝细胞的分化并改善肝损伤。

Sodium Butyrate Pre-Treatment Enhance Differentiation of Bone Marrow Mesenchymal Stem Cells (BM-MSCs) into Hepatocytes and Improve Liver Injury.

机构信息

Department of Radiology, Second Xiangya Hospital of Central South University, Changsha, Hunan, 410011, China.

Department of Radiology, Second People's Hospital of Hunan Province, Changsha, Hunan, 410007, China.

出版信息

Curr Mol Med. 2022;22(7):663-674. doi: 10.2174/1566524021666211014161716.

Abstract

OBJECTIVE

The treatment of liver failure by stem cell transplantation has attracted growing interest. Herein, we aim to explore the role of sodium butyrate (NaB) in the hepatic differentiation of bone marrow mesenchymal stem cells (BM-MSCs) under liver-specific factors induction in vitro and vivo.

MATERIALS & METHODS: We isolated BM-MSCs from the mononuclear cell fraction of rabbit bone marrow samples and identified the cells by Immunophenotypic analysis. We investigated the effects of different concentrations and induction conditions. The histone deacetylase inhibitor NaB induced hepatic differentiation of BM-MSCs under liverspecific factors induction in vitro. Morphological features, liver-specific gene and protein expression, and functional analyses in vitro and vivo were performed to evaluate the hepatic differentiation of BM-MSCs.

RESULTS

Our results showed that pre-treated NaB inhibited the expression of the liverspecific protein in a dose-dependent manner. The induction efficiency of NaB with 24h pre-treatment was higher than that of NaB continuous intervention. 0.5 mM 24h NaB pre-treated cells can improve liver tissue damage in vivo. The liver ALB, AAT, and the serum TP were significantly increased, while the serum ALT was significantly reduced.

CONCLUSION

Continuous NaB treatment can inhibit BM-MSCs proliferation in a dosedependent manner at a certain concentration range. 0.5 mM 24h pre-treatment of NaB enhanced differentiation of BM-MSCs into hepatocytes and improved liver injury in vitro and vivo.

摘要

目的

干细胞移植治疗肝衰竭的研究受到越来越多的关注。本研究旨在探讨丁酸钠(NaB)在肝特异因子诱导下体外和体内骨髓间充质干细胞(BM-MSCs)向肝系分化中的作用。

材料与方法

我们从兔骨髓单个核细胞中分离 BM-MSCs,并通过免疫表型分析鉴定细胞。我们研究了不同浓度和诱导条件的影响。组蛋白去乙酰化酶抑制剂 NaB 在肝特异因子诱导下诱导 BM-MSCs 向肝系分化。体外和体内进行形态学特征、肝特异基因和蛋白表达以及功能分析,以评估 BM-MSCs 的肝向分化。

结果

我们的结果表明,NaB 预处理以剂量依赖性方式抑制肝特异性蛋白的表达。24h 预处理 NaB 的诱导效率高于 NaB 持续干预。0.5mM 24h NaB 预处理细胞可改善体内肝组织损伤。肝组织 ALB、AAT 和血清 TP 明显升高,血清 ALT 明显降低。

结论

在一定浓度范围内,连续 NaB 处理可呈剂量依赖性抑制 BM-MSCs 的增殖。0.5mM 24h NaB 预处理增强了 BM-MSCs 向肝细胞的分化,并改善了体外和体内的肝损伤。

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