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胰岛素样生长因子-I 促进人脂肪组织来源的干细胞向肝系分化。

Insulin-like growth factor-I promotes hepatic differentiation of human adipose tissue-derived stem cells.

机构信息

Endocrinology and Metabolism Research Center, Hormozgan University of Medical Sciences, Bandar Abbas, Iran.

Department of Clinical Biochemistry, Faculty of Medicine, Hormozgan University of Medical Sciences, Bandar Abbas, Iran.

出版信息

Cell Biol Int. 2019 May;43(5):476-485. doi: 10.1002/cbin.11113. Epub 2019 Mar 12.

Abstract

There are numerous studies which provide support for the use of human adipose tissue-derived stem cells (hASCs) to generate hepatocyte-like cells. However, the produced cells exhibit only a certain level of differentiation, mainly due to inefficient induction conditions. Therefore, based on the important role of insulin-like growth factor (IGF-I) in hepatic function and development, in the current study we evaluated the differentiation efficacy of the mentioned factor to induce hASCs into functional hepatocyte-like cells. To investigate this, using a two-step protocol, hASCs were treated with a combination of HGF, Dex, and OSM in the presence or absence of IGF-I up to 21 days. Hepatic differentiation was evaluated by analyzing specific hepatocyte markers at different time points of differentiation induction. Increased expression of hepatocyte-specific genes including ALB, AFP, CK18, and HNF4a, downregulation of bile duct cells marker (CK19), the higher number of ALB positive cells, increased urea production together with higher glycogen deposit was observed upon the treatment of hASCs with the induction medium containing IGF-I compared to the other treatment. In conclusion, our findings suggest IGF-I as a potent inducer of hepatic differentiation of hASCs and its potential to generate more functional hepatocyte-like cells.

摘要

有大量研究支持使用人脂肪组织源性干细胞(hASCs)生成肝样细胞。然而,所产生的细胞仅表现出一定程度的分化,主要是由于诱导条件效率低下。因此,基于胰岛素样生长因子(IGF-I)在肝功能和发育中的重要作用,在本研究中我们评估了该因子将 hASCs 诱导分化为功能性肝样细胞的效果。为了研究这一点,我们使用两步法,在存在或不存在 IGF-I 的情况下,用 HGF、Dex 和 OSM 联合处理 hASCs 长达 21 天。通过在不同的分化诱导时间点分析特定的肝细胞标记物来评估肝分化。与其他处理相比,用含有 IGF-I 的诱导培养基处理 hASCs 后,观察到肝细胞特异性基因(包括 ALB、AFP、CK18 和 HNF4a)的表达增加,胆管细胞标记物(CK19)下调,ALB 阳性细胞数量增加,尿素生成增加,糖原沉积增加。综上所述,我们的研究结果表明 IGF-I 是 hASCs 肝分化的有效诱导剂,具有生成更多功能性肝样细胞的潜力。

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