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Establishment and characterization of an immortalized human hepatocyte line for the development of bioartificial liver system

机译:建立和表征永生化人类肝细胞系以发展生物人工肝系统

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摘要

For further research and application of Bioartificial liver systems (BAL), active proliferation capacity and full hepatic functionality of the biomaterials is mandatory. However, there are still no suitable cell lines meeting the requirements for an ideal cell source in BAL development that makes it necessary to explore other sources. Here, we constructed a new cell line derived from well-differentiated hepatocellular carcinoma tissues designated NHBL2. Immunol staining showed that NHBL2 possessed the capacity of synthesizing albumin and CYP2E1 and quantitative analysis showed that the albumin synthesis ability of NHBL2 was comparable to C3A while urea production was highly abundant of NHBL2 compared with that of C3A. Using gene expression microarray analysis, we found that the expression levels of a set of genes encoding Phase I and Phase II metabolizing enzymes as well as many others related to common bioconversion and metabolic processes were significantly higher in NHBL2 cell line than that in C3A. Moreover, functional optimization assay in Matrigel showed obvious improvements of liver-related function level and a low malignance of this cell line. These findings indicated that NHBL2 possessed relatively attractive and full hepatic functionality that might be a potential cell line for BAL development.
机译:为了进一步研究和应用生物人工肝系统(BAL),必须具有生物材料的主动增殖能力和完整的肝功能。但是,仍然没有合适的细胞系能够满足BAL开发中理想细胞来源的要求,因此有必要探索其他来源。在这里,我们构建了一个新的细胞系,该细胞系衍生自命名为NHBL2的分化良好的肝细胞癌组织。免疫染色表明,NHBL2具有合成白蛋白和CYP2E1的能力,定量分析表明,NHBL2的白蛋白合成能力与C3A相当,而NHBL2的尿素产量比C3A高。使用基因表达微阵列分析,我们发现NHBL2细胞系中编码一组I期和II期代谢酶以及许多与常见生物转化和代谢过程相关的基因的表达水平显着高于C3A。此外,在Matrigel中进行的功能优化分析表明,与肝脏相关的功能水平明显改善,并且该细胞系的恶性程度较低。这些发现表明,NHBL2具有相对诱人和完整的肝功能,可能是BAL发育的潜在细胞系。

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