Department of Toxicology, Center for Pharmaceutical Research (CePhaR), Vrije Universiteit Brussel (VUB), Laarbeeklaan 103, 1090 Brussels, Belgium.
Toxicol In Vitro. 2014 Feb;28(1):113-9. doi: 10.1016/j.tiv.2013.06.014. Epub 2013 Jun 29.
Stem cell technology could offer a unique tool to develop human-based in vitro liver models that are applicable for testing of potential liver toxicity early during drug development. In this context, recent research has indicated that human Wharton's Jelly-derived mesenchymal stem cells (hWJs) represent an interesting stem cell population to develop human hepatocyte-like cells. Here, an in-depth analysis of the expression of liver-specific transcription factors and other key hepatic markers in hWJs is evaluated at both the mRNA and protein level. Our results reveal that transcription factors that are mandatory to acquire and maintain an adult hepatic phenotype (HNF4A and HNF1A), as well as adult hepatic markers (ALB, CX32, CYP1A1, CYP1A2, CYP2B6 and CYP3A4) are not expressed in hWJs with the exception of K18. On the contrary, transcription factors involved in liver development (GATA4, GATA6, SOX9 and SOX17) and liver progenitor markers (DKK1, DPP4, DSG2, CX43 and K19) were found to be highly expressed in hWJs. These findings provide additional indication that hWJs could be a promising stem cell source to generate hepatocyte-like cells necessary for the development of a functional human-based in vitro liver model.
干细胞技术为开发适用于药物研发早期潜在肝毒性测试的基于人类的体外肝脏模型提供了独特的工具。在这方面，最近的研究表明，人脐带来源间充质干细胞（hWJ）是开发人肝细胞样细胞的一种有趣的干细胞群体。在这里，我们在 mRNA 和蛋白质水平上深入分析了 hWJ 中肝脏特异性转录因子和其他关键肝脏标志物的表达。我们的结果表明，除了 K18 之外，获得和维持成人肝表型所必需的转录因子（HNF4A 和 HNF1A）以及成人肝标志物（ALB、CX32、CYP1A1、CYP1A2、CYP2B6 和 CYP3A4）在 hWJ 中并不表达。相反，与肝脏发育相关的转录因子（GATA4、GATA6、SOX9 和 SOX17）和肝脏祖细胞标志物（DKK1、DPP4、DSG2、CX43 和 K19）在 hWJ 中被发现高度表达。这些发现进一步表明，hWJ 可能是一种有前途的干细胞来源，可以生成用于开发功能性基于人类的体外肝脏模型所需的肝细胞样细胞。
