Centre for Biotechnology and Biomedicine, BBZ, University of Leipzig, Germany.
J Tissue Eng Regen Med. 2012 Jun;6(6):486-96. doi: 10.1002/term.453. Epub 2011 Jul 13.
Little is known about how cells respond to different biomaterials at the molecular level. Biomaterials could stimulate specific cellular responses at the molecular level, such as activation of signalling pathways that control gene activity involved in the maintenance, growth and functional regeneration of liver tissue in vitro. This aspect is an important step in liver tissue engineering. Currently, there are no data available concerning the modulation of cellular genomic response by using synthetic membranes in a bioartificial system. For the first time we investigated gene expression profiles of primary hepatocytes cultured on different substrates: collagen sandwich, native and NH(3) plasma-grafted PEEK-WC-PU membranes. Gene expression in cell suspension prepared after cell isolation was used as a control. Generally, microarray data revealed that the expression of the majority of genes remained unchanged compared to the control. Among 31 000 genes, 52 were significantly changed: 20 were upregulated and 32 downregulated. There were similar changes in gene expression of hepatocytes cultured in the membranes and collagen sandwich. However, some genes involved in the cell proliferation and functional metabolic pathways are more expressed in cells cultured on the membranes and especially on the functionalized ones. Both membranes sustained liver functions at the molecular level, demonstrating their suitability for the reconstruction of liver and as a toxicogenomic tool to predict the liver response to novel drugs.
目前对于细胞在分子水平上如何响应不同的生物材料知之甚少。生物材料可以在分子水平上刺激特定的细胞反应,例如激活信号通路,这些信号通路可以控制参与体外维持、生长和功能再生的基因活性。这是肝组织工程的重要步骤。目前,关于在生物人工系统中使用合成膜来调节细胞基因组反应,尚无数据。我们首次研究了在不同底物上培养的原代肝细胞的基因表达谱:胶原夹层、天然和 NH(3)等离子体接枝 PEEK-WC-PU 膜。细胞分离后细胞悬液的基因表达用作对照。一般来说,微阵列数据显示,与对照相比,大多数基因的表达保持不变。在 31000 个基因中,有 52 个基因的表达发生了显著变化:20 个上调,32 个下调。在膜和胶原夹层中培养的肝细胞的基因表达也有类似的变化。然而,一些参与细胞增殖和功能代谢途径的基因在培养于膜上的细胞中表达更为明显,尤其是在功能化的膜上。两种膜都在分子水平上维持了肝脏功能,证明它们适用于肝脏的重建,并且是一种毒理基因组学工具,可以预测肝脏对新型药物的反应。