Vinken Mathieu, Papeleu Peggy, Snykers Sarah, De Rop Evelien, Henkens Tom, Chipman James Kevin, Rogiers Vera, Vanhaecke Tamara
Department of Toxicology, Vrije Universiteit Brussel (VUB), Brussels, Belgium.
Crit Rev Toxicol. 2006 Apr;36(4):299-318. doi: 10.1080/10408440600599273.
In liver, like in other multicellular systems, the establishment of cellular contacts is a prerequisite for normal functioning. In particular, well-defined cell junctions between hepatocytes, including adherens junctions, desmosomes, tight junctions, and gap junctions, are known to play key roles in the performance of liver-specific functionality. In a first part of this review article, we summarize the current knowledge concerning cell junctions and their roles in hepatic (patho)physiology. In a second part, we discuss their relevance in liver-based in vitro modeling, thereby highlighting the use of primary hepatocyte cultures as suitable in vitro models for preclinical pharmaco-toxicological testing. We further describe the actual strategies to regain and maintain cell junctions in these in vitro systems over the long-term.
在肝脏中,与其他多细胞系统一样,细胞间接触的建立是正常功能发挥的前提条件。特别是,肝细胞之间明确的细胞连接,包括黏着连接、桥粒、紧密连接和缝隙连接,已知在肝脏特异性功能的发挥中起关键作用。在这篇综述文章的第一部分,我们总结了关于细胞连接及其在肝脏(病理)生理学中作用的当前知识。在第二部分中,我们讨论它们在基于肝脏的体外模型中的相关性,从而突出原代肝细胞培养作为临床前药物毒理学测试合适体外模型的应用。我们进一步描述了在这些体外系统中长期恢复和维持细胞连接的实际策略。