Primary hepatocytes outperform Hep G2 cells as the source of biotransformation functions in a bioartificial liver.
Primary hepatocytes outperform Hep G2 cells as the source of biotransformation functions in a bioartificial liver.
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发表时间：
1994-07
影响因子：
9
通讯作者：
S. Nyberg;R. Remmel;H. Mann;M. Peshwa;Wei-Shou Hu;F. Cerra
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文献类型：
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作者：
S. Nyberg;R. Remmel;H. Mann;M. Peshwa;Wei-Shou Hu;F. Cerra
目的比较凝胶包埋型生物人工肝体外应用过程中转化人肝细胞（Hep G2）和原代大鼠肝细胞的代谢活性。背景含有转化肝细胞或原代肝细胞的生物人工肝装置的临床试验已经开始。在类似条件下，在生物人工肝中比较转化肝细胞和原代肝细胞的研究以前尚未报道。方法将凝胶包埋型生物人工肝装置分别接种1亿个细胞、Hep G2细胞株（n = 4）和大鼠肝细胞（n = 16），体外培养60 d。结果Hep G2细胞在凝胶包埋结构中生长至汇合，倍增时间为20 ± 3小时。大鼠肝细胞在所有类别的生物转化（包括尿素生成）中均显著优于汇合时的Hep G2细胞（3.5 ± 0.7 vs. 0.3 ± 0.1 mumol/hr，p < 0.05），葡萄糖醛酸化（630 +/- 75 vs. 21 +/- 2 nmol/hr，p < 0.005）、硫酸化（59 +/- 13 vs. 5 +/- 2 nmol/hr，p < 0.05）和氧化（233 +/- 38 vs. < 1 nmol/hr，p < 0.005）。在一项实验结束时，在生物人工肝的毛细血管外隔室中发现了Hep G2细胞，类似于临床应用期间的患者隔室。结论原代大鼠肝细胞作为生物人工肝的肝功能来源上级Hep G2细胞系，并避免了肿瘤从生物人工肝转移到患者循环中的潜在风险。
OBJECTIVE Metabolic activity of transformed human liver (Hep G2) cells and primary rat hepatocytes were compared during in vitro application of a gel entrapment bioartificial liver. BACKGROUND Clinical trials of bioartificial liver devices containing either transformed liver cells or primary hepatocytes have been initiated. A study comparing transformed liver cells and primary hepatocytes in a bioartificial liver under similar conditions has not been reported previously. METHODS Gel entrapment bioartificial liver devices were inoculated with 100 million cells, Hep G2 cell line (n = 4), or rat hepatocytes (n = 16), and studied for up to 60 days of in vitro cultivation. RESULTS Hep G2 cells grew to confluence within the gel entrapment configuration with a doubling time of 20 +/- 3 hours. Rat hepatocytes significantly outperformed Hep G2 cells at confluence in all categories of biotransformation, including ureagenesis (3.5 +/- 0.7 vs. 0.3 +/- 0.1 mumol/hr, p < 0.05), glucuronidation (630 +/- 75 vs. 21 +/- 2 nmol/hr, p < 0.005), sulfation (59 +/- 13 vs. 5 +/- 2 nmol/hr, p < 0.05), and oxidation (233 +/- 38 vs. < 1 nmol/hr, p < 0.005). At the conclusion of one experiment, Hep G2 cells were found in the extracapillary compartment of the bioartificial liver, analogous to the patient's compartment during clinical application. CONCLUSIONS Primary rat hepatocytes were superior to the Hep G2 cell line as the source of hepatic function in a bioartificial liver and avoided the potential risk of tumor transmigration from the bioartificial liver into the patient's circulation.