Davoodian Nahid, Lotfi Abbas S, Soleimani Masoud, Ghaneialvar Hori
Molecular Medicine Research Center, Hormozgan Health Institute, Hormozgan University of Medical Sciences, Bandar Abbas, Iran.
Department of Clinical Biochemistry, Faculty of Medical Science, Tarbiat Modares University, Tehran, Iran.
Cell Biol Int. 2017 Oct;41(10):1083-1092. doi: 10.1002/cbin.10836. Epub 2017 Aug 29.
Human adipose tissue-derived stem cells (hADSCs) have been considered as a promising source for cell therapy of liver diseases due to their accessibility, abundance, and expression of hepatocyte markers. Currently, the important role of certain microRNAs (miRNAs) has been reported during hepatic differentiation of stem cells. However, the combination effect of miRNAs on hepatic differentiation of these cells needs to be more investigated. The present study seeks to determine whether the combination of miRNAs can enhance hepatic differentiation of hADSCs in the absence of any other stimulation. First, lentiviral transduction was used to overexpress miR-122 and silence d let-7f in hADSCs for up to 21 days. Then, hepatic functionality was evaluated by analyzing specific hepatocyte genes and biochemical markers at different time points of differentiation induction. Stable miR-122 overexpression and let-7f silencing together in hADSCs resulted in increased expression of hepatocyte markers including ALB, AFP, CK18, CK19, and HNF4a. In addition, urea and albumin production, immunocytochemistry, and glycogen staining confirmed that the treated cells differentiated toward hepatocyte-like cells. Therefore, our findings demonstrate the possibility of using microRNAs to induce hADSCs into functional hepatocyte-like cells.
人脂肪组织来源的干细胞（hADSCs）因其易于获取、数量丰富以及表达肝细胞标志物，而被视为肝病细胞治疗的一个有前景的细胞来源。目前，已有报道某些微小RNA（miRNAs）在干细胞肝分化过程中发挥重要作用。然而，miRNAs对这些细胞肝分化的联合作用尚需更多研究。本研究旨在确定在无任何其他刺激的情况下，miRNAs的联合使用是否能增强hADSCs的肝分化。首先，采用慢病毒转导在hADSCs中过表达miR-122并沉默let-7f，持续21天。然后，在分化诱导的不同时间点，通过分析特定的肝细胞基因和生化标志物来评估肝脏功能。hADSCs中miR-122的稳定过表达和let-7f的共同沉默导致肝细胞标志物包括白蛋白（ALB）、甲胎蛋白（AFP）、细胞角蛋白18（CK18）、细胞角蛋白19（CK19）和肝细胞核因子4α（HNF4a）的表达增加。此外，尿素和白蛋白生成、免疫细胞化学以及糖原染色证实，处理后的细胞向肝细胞样细胞分化。因此，我们的研究结果证明了利用微小RNA将hADSCs诱导为功能性肝细胞样细胞的可能性。
