ULTRASOUND IRRADIATION COMBINED WITH HEPATOCYTE GROWTH FACTOR ACCELERATE THE HEPATIC DIFFERENTIATION OF HUMAN BONE MARROW MESENCHYMAL STEM CELLS
ULTRASOUND IRRADIATION COMBINED WITH HEPATOCYTE GROWTH FACTOR ACCELERATE THE HEPATIC DIFFERENTIATION OF HUMAN BONE MARROW MESENCHYMAL STEM CELLS
复制标题
超声波照射结合肝细胞生长因子加速人骨髓间充质干细胞的肝脏分化
DOI：
10.1016/j.ultrasmedbio.2018.01.005
复制
发表时间：
2018-05-01
影响因子：
2.9
通讯作者：
Du, Lianfang
中科院分区：
文献类型：
--
作者：
Li, Fan;Liu, Yang;Du, Lianfang
本研究探讨超声辐照对肝细胞生长因子（HGF）诱导的人骨髓间充质干细胞（hBMSCs）向肝细胞分化的影响及其可能机制。我们处理hBMSCs，使用HGF和不使用US照射。分析细胞活力和干细胞表面标志物。分别于治疗后第1、3、5天检测肝细胞样细胞标志物和功能标志物甲胎蛋白（alpha FP/AFP）、细胞角蛋白18（CK 18）、白蛋白（ALB）和糖原含量。Wnt/β-catenin信号通路的参与也进行了评估。结果表明，在1.0 W/cm ~ 2或1.5 W/cm ~ 2的超声处理30 s或60 s条件下，细胞活力良好，并产生干细胞分化。在第5天，与HGF组和对照组相比，US处理组的AFP、CK 18、ALB表达和糖原含量在信使核糖核酸和蛋白水平上均显著升高（均p < 0.05）。在所有US处理组中，（1.5 W/cm（2）持续60 s）组中特异性肝脏标志物的表达水平最高。超声照射后，Wnt 1、β-Catenin、c-Myc和Cyclin D1均显著升高（均p < 0.05），抑制剂ICG-001可明显抑制c-Myc和Cyclin D1的升高（p < 0.05，p < 0.05），与ALB、CK 18表达和糖原含量的降低（均p < 0.05）相一致。结论：超声辐照能安全、简便、可控地促进HGF介导的hBMSCs体外分化。Wnt/beta-catenin信号通路的激活参与了这一过程。超声辐照可作为干细胞分化研究和应用的一种潜在有利工具。（电子邮件：lianfang_du@126.com）（c）2018年世界医学和生物学超声联合会。All rights reserved.
This study investigated the impact of ultrasound (US) irradiation on the hepatic differentiation of human bone marrow mesenchymal stem cells (hBMSCs) induced by hepatocyte growth factor (HGF) and the possible mechanisms. We treated hBMSCs, using HGF with and without US irradiation. Cell viability and stem cell surface markers were analyzed. Hepatocyte-like cell markers and functional markers including alpha-fetoprotein (alpha FP/AFP), cytokeratin 18 (CK18), albumin (ALB) and glycogen content were analyzed at the time point of day 1, 3 and 5 after treatment. The involvement of Wnt/beta-catenin signaling pathway was evaluated as well. The results showed that the US treatment at 1.0 W/cm2 or 1.5 W/cm(2) for 30 s or 60 s conditions yielded favorable cell viability and engendered stem cell differentiation. At day 5, the expressions of AFP, CK18, ALB and the glycogen content were significantly elevated in the US-treated group at both messenger ribonucleic acid and protein levels (all p < 0.05), in comparison with HGF and control groups. Among all the US treated groups, the expression levels of specific hepatic markers in the (1.5 W/cm(2) for 60 s) group were the highest. Furthermore, Wnt1, beta-Catenin, c-Myc and Cyclin D1 were significantly increased after US irradiation (all p < 0.05), and the enhancements of c-Myc and Cyclin D1 could be obviously impaired by the inhibitor ICG-001 (p < 0.05, p < 0.05), in accordance with decreased ALB and CK18 expression and glycogen content (all p < 0.05). In conclusion, US irradiation was able to promote the hBMSCs' differentiation mediated by HGF in vitro safely, easily and controllably. The activation of Wnt/beta-catenin signaling pathway was involved in this process. US irradiation could serve as a potentially beneficial tool for the research and application of stem cell differentiation. (E-mail: lianfang_du@126.com) (c) 2018 World Federation for Ultrasound in Medicine & Biology. All rights reserved.