کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2602553 1133783 2012 8 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Optimization of the HepaRG cell model for drug metabolism and toxicity studies
موضوعات مرتبط
علوم زیستی و بیوفناوری علوم محیط زیست بهداشت، سم شناسی و جهش زایی
پیش نمایش صفحه اول مقاله
Optimization of the HepaRG cell model for drug metabolism and toxicity studies
چکیده انگلیسی

The HepaRG cell line is the first human cell line able to differentiate in vitro into mature hepatocyte-like cells. Our main objective within the framework of the EEC-LIINTOP project was to optimize the use of this cell line for drug metabolism and toxicity studies, especially after repeat treatments. The main results showed that differentiated HepaRG cells: (i) retained their drug metabolism capacity (major CYPs, phase 2 enzymes, transporters and nuclear receptors) and responsiveness to prototypical inducers at relatively stable levels for several weeks at confluence. The levels of several functions, including some CYPs such as CYP3A4, were dependent on the addition of dimethyl sulfoxide in the culture medium; (ii) sustained the different types of chemical-induced hepatotoxicity, including steatosis, phospholipidosis and cholestasis, after acute and/or repeat treatment with reference drugs. In particular, drug-induced vesicular steatosis was demonstrated in vitro for the first time. In conclusion, our results from the LIINTOP project, together with other studies reported concomitantly or more recently in the literature, support the conclusion that the metabolically competent human HepaRG cells represent a surrogate to primary human hepatocytes for investigating drug metabolism parameters and both acute and chronic effects of xenobiotics in human liver.


► This review summarizes recent data on the performances of the human HepaRG cell line.
► The HepaRG cell line is the first human cell line able to differentiate in vitro into mature hepatocytes.
► These cells retain drug metabolism capability and responsiveness to inducers for several weeks at confluence.
► HepaRG cells are also suitable for studies on drug-induced liver injury.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Toxicology in Vitro - Volume 26, Issue 8, December 2012, Pages 1278–1285
نویسندگان
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