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Dear all,
Does anybody have experiences with HepaRG cells? It is an
immortalized hepatocytes which could be used in CYP induction and
transporter study. I heard it is quite difficult to handle and
transporter expression can be very variable and especially problematic
for NTCP. Any comments on that are highly appreciated.
Guoyu
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The following message was posted to: PharmPK
You may find the following papers useful:
Kanebratt KP and Andersson TB (2008) HepaRG cells as an in vitro model
for
evaluation of cytochrome P450 induction in humans. Drug Metab Dispos
36:137-145.
Le Vee M, Jigorel E, Glaise D, Gripon P, Guguen-Guillouzo C and Fardel O
(2006) Functional expression of sinusoidal and canalicular hepatic drug
transporters in the differentiated human hepatoma HepaRG cell line.
Eur J
Pharm Sci 28:109-117.
McGinnity DF, Zhang G, Kenny J, Hamilton G, Otmani S, Stams K, Haney S,
Brassil P, Stresser DM and Riley RJ (2009) Evaluation of multiple in
vitro
systems for assessment of CYP3A4 Induction in Drug Discovery: Human
hepatocytes, PXR reporter gene, Fa2N-4 and HepaRG cells. Drug Metab
Dispos
37:1259-1268.
Regards
Masoud
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Hi Guoyu,
HepaRG cells are originally derived form female patient suffering from
hepatocarcinoma.
Crucial factor for the differentiation of cells is the concentration
of DMSO, insulin and hydrocortison in the culture medium.
The level of expression of NTCP will be lower as compare to primary
hepatocytes culture but it will be considerably higher than that of
other hepatoma cell lines. You can check the transport of TC in the
presence and absence of Na+ for the assessment of NTCP level.
You may find following reference useful:
1) Carine B. Lambert , Catherine Spire, Marie-Pierre Renaud, Nancy
Claude, Andre Guillouzo, Reproducible chemical-induced changes in gene
expression profiles in human hepatoma HepaRG cells under various
experimental conditions, Toxicology in Vitro 23 (2009) 466-475
2) Infection of a human hepatoma cell line by hepatitis B virus.
Gripon, P., Rumin, S., Urban, S., Le Seyec, J., Glaise, D., Cannie,
I., Guyomard, C., Lucas, J., Trepo, C., Guguen-Guillouzo, C., Proc.
Natl. Acad. Sci. U.S.A. 99, (2002)15655-15660.
Thanks and Regards
Rhishikesh Thakare
Advinus Therapeutics, Pune, India.
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Yes Rhishi,
But I assume the interspecies NTCP and ASBT polymorphism across the
HepaRG cells is something independent of the externous environment
(like the culture medium). The expression of hNTCP gene is more
crucial to characterize to make the yardstick for the particular batch
before the study.
Thank You
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