Hepatocyte cell line

Carroll SS, Olsen DB (2006) Nucleoside analog inhibitors of hepatitis C vims rephcation. Infect Disord Dmg Targets (Formerly Current Drag Targets - Infectious) 6 17-29 CasteU JV, lover R, Martinez-Jimenez CP, Gomez-Lechon MJ (2006) Hepatocyte cell lines their use, scope and limitations in dmg metabolism studies. Expert Opin Drag Metab Toxicol 2 183-212... 

Mills, J.B., Rose, K.A., Sadagopan, N., Sahi, J. and de Morais, S.M. (2004) Induction of drug metabolism enzymes and MDR1 using a novel human hepatocyte cell line. The Journal of Pharmacology and Experimented Therapeutics, 309, 303-309. 

In vitro assays are increasingly being used. Some of the reasons are cost, availability of more rapid results, and avoidance of negative publicity. Assays such as cytochrome P-450 enzymes, the Ames test, and the mouse lymphoma tk test are in vitro methods. For absorption studies, Caco-2 (Exhibit 5.9) and Madin-Darby canine kidney cell assays are now routinely used. Hepatocyte cell lines with metabolism capacity are being developed to test drug metabolism and toxicity. All these examples show that, where possible, pharmaceutical firms are gradually dispensing with animal studies. 

Immortalized hepatocytes A major drawback of the use of primary hepatocytes is that hepatocytes can not be expanded in culture. To overcome this problem, researchers have embarked on the immortalization of primary hepatocyte cultures (e.g. Bayad et al. 1991 Li et al. 2005). Currently, immortalized human hepatocyte cell lines are available commercially and may represent convenient screening experimental systems for enzyme induction studies. Unfortunately, at the time of this writing, there are no peer-reviewed publications on the application of human immortalized hepatocytes in induction studies. It is important to ensure that the induced isoforms in the cell lines are the mature P450 isoforms rather than the embryonic forms. For instance, the use of HepG2 cells may not be appropriate as the embryonic P450 isoforms CYP1A1... 

Another independent approach to the mapping of apoB on the lipoprotein surface arose unexpectedly during studies on the mechanism of lipoprotein assembly in hepatocyte cell lines, and this will be described next. 

A remarkable observation was made by Yao et al. (1991), who expressed a homologous series of C-terminal truncated apoB molecules in stably transfected McArdle 7777 cells, a rat hepatocyte cell line. Plotting the buoyant density of the secreted lipoproteins as a function of the logarithm of the number of amino acid residues, they noticed a linear relationship between these two quantities, implying that the lipoprotein density was inversely proportional to the apoB size. Evidently some fundamental architectural principle was being explored in their studies. 

The permanent hepatocyte cell lines that have been studied, HepG2 and McArdle 7777 cells, are defective and do not make the large VLDLs characteristic of normal liver. Instead, they secrete the small, triglyceride-rich lipoproteins described in the previous section of this review. We will call these primary lipoprotein particles. 

Acetaminophen causes cytotoxicity in several cell types however, the most widely studied cytotoxicity of acetaminophen is in primary hepatocytes or hepatocyte cell lines. 

The development of differentiation protocols for human iPSC-derived hepatocytes requires benchmarking studies against primary human hepatocytes and commonly used hepatocyte cell lines. A recent study compared human iPSC-derived hepatocytes (hiPSC-Hep) with primary human hepatocytes and the HepG2 cell line... 

Youdim, K. A., Tyman, C. A., Jones, B. C., and Hyland, R. (2007) Induction of cytochrome P450 assessment in an immortalized human hepatocyte cell line (Fa2N4) using a novel higher throughput cocktail assay. Drug Metab. Dispos. 35, 275-282. 

Guilhot S, Miller T, Comman G, Isom HC (1996) Apoptosis induced by tumor necrosis factor-alpha in rat hepatocyte cell lines expressing Hepatitis B virus. Am J Pathol 148 801-814... 

Benoit, G.G., C.F. Naud, M.A. Simard, and A.L. Astier (1997). Noninterference of cytochrome P4501A2 in the cytotoxicity of tacrine using genetically engineered V79 Chinese hamster cells for stable expression of the human or rat isoform and two human hepatocyte cell lines. Biochem. Pharmacol. 53, 423-427. 

Selden, C., Shariat, A., McCloskey, P., Ryder, T., Roberts, E., and Hodgson, H. (1999), Three-dimensional in vitro cell culture leads to a mark upregulation of cell function in human hepatocyte cell lines An important tool for the development of a bioartificial liver machine, Ann. N.Y. Acad. Sci. 875 353-363. 

Kondo A, Miyazaki M, Pu H, Gao C, Namba M (1999) Establishment and cellular characteristics of a hepatocyte cell line (OUMS-31) derived from an acatalasemic mouse. In Vitro Cell Dev Biol Anim 35 155-158... 

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