Filippi Céline, Keatch Steven A, Rangar Deepa, Nelson Leonard J, Hayes Peter C, Plevris John N
Department of Hepatology, Chancellor's Building, 49 Little France Crescent, Edinburgh EH16 4SB Scotland, UK.
J Hepatol. 2004 Oct;41(4):599-605. doi: 10.1016/j.jhep.2004.06.012.
BACKGROUND/AIMS: The use of cell lines in bioartificial liver support systems (BALSS) to treat fulminant hepatic failure (FHF) is hindered by their reduced metabolic functions, which could be further decreased by the patient's serum/plasma. Hence, the aim of this study was to (i) test the effect of the FHF serum on C3A cell metabolism; (ii) precondition the cells to improve their metabolic capacity.
C3A cells were preconditioned in a medium developed at the University of Edinburgh (UoE) or a 10% FHF serum medium. Metabolism capacity was assessed on days 3, 7 and 10 and compared with primary porcine hepatocytes. Preconditioned-cell metabolism was reassessed after (i) passage and (ii) incubation with 10% FHF serum.
UoE-preconditioned cells showed time-dependent increase in gluconeogenesis (500%), ureogenesis (200%), galactose elimination (240%) albumin synthesis (250%). These results were in the same order of magnitude as the ones obtained with primary porcine hepatocytes and were further enhanced by cell passage. UoE-preconditioning prevented the decrease of metabolism induced by acute incubation with FHF serum on control C3A cells. Preconditioning with FHF serum did not improve cell metabolism.
Cell preconditioning with UoE-medium increases metabolic capacity and would greatly improve BALSS efficacy.
背景/目的：生物人工肝支持系统（BALSS）中使用细胞系治疗暴发性肝衰竭（FHF）受到其代谢功能降低的阻碍，而患者的血清/血浆可能会进一步降低其代谢功能。因此，本研究的目的是：（i）测试FHF血清对C3A细胞代谢的影响；（ii）对细胞进行预处理以提高其代谢能力。
C3A细胞在爱丁堡大学（UoE）研发的培养基或10%FHF血清培养基中进行预处理。在第3、7和10天评估代谢能力，并与原代猪肝细胞进行比较。在（i）传代后和（ii）与10%FHF血清孵育后重新评估预处理细胞的代谢。
UoE预处理的细胞在糖异生（500%）、尿素生成（200%）、半乳糖消除（240%）、白蛋白合成（250%）方面呈时间依赖性增加。这些结果与原代猪肝细胞获得的结果处于同一数量级，并通过细胞传代进一步增强。UoE预处理可防止对照C3A细胞急性孵育FHF血清所诱导的代谢降低。用FHF血清预处理并不能改善细胞代谢。
用UoE培养基对细胞进行预处理可提高代谢能力，并将大大提高BALSS的疗效。
