Related Experiment Video
Updated: May 31, 2026
05:49
Robust Generation of Hepatocyte-like Cells from Human Embryonic Stem Cell Populations
Published on: October 26, 2011
The HepaRG cell line is suitable for bioartificial liver application.
Ruurdtje Hoekstra1, Geert A A Nibourg, Tessa V van der Hoeven
1Surgical Laboratory, Academic Medical Center, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands. r.hoekstra@amc.uva.nl
Summary
HepaRG cells demonstrate robust metabolic and synthetic functions without dimethyl sulfoxide (DMSO), while drug metabolism is enhanced with DMSO. Combining both conditions optimizes hepatic functionality for bioartificial liver applications.
Area of Science:
- Hepatology and cell biology
- Biotechnology and regenerative medicine
Background:
- Bioartificial liver (BAL) applications require cells with ammonia elimination, drug metabolism, and protein synthesis capabilities.
- HepaRG cells, a human cell line, differentiate into hepatocyte and biliary epithelial-like cells, showing potential for liver tissue engineering.
Purpose of the Study:
- To evaluate the suitability of HepaRG cells for BAL by assessing their hepatic functions.
- To investigate the impact of dimethyl sulfoxide (DMSO) and carbamoyl-glutamate (CG) on HepaRG cell functionality.
Main Methods:
- HepaRG cells were cultured with and without DMSO, with or without CG, in the presence of (15)NH(4)Cl.
- Hepatocyte-specific functions were assessed at transcriptomic and biochemical levels, including ureagenesis, ammonia/galactose elimination, albumin synthesis, and cytochrome P450 (CYP) activity.
- Cell damage parameters and immunostainings were performed.
Main Results:
- Absence of DMSO (-DMSO) enhanced ureagenesis, ammonia/galactose elimination, and albumin, glutamine synthetase, and carbamoylphosphate synthetase (CPS) transcript levels.
- DMSO treatment (+DMSO) increased CYP transcript levels and CYP3A4 activity but also induced cell damage and repressed hepatic functionality.
- CG preconditioning significantly increased (15)NH(4)Cl conversion to (15)N-urea in -DMSO cultures.
- Both +DMSO and -DMSO cultures achieved primary hepatocyte levels for ammonia elimination, apolipoprotein A-1 production, and CYP3A4, CYP2B6, and albumin transcription.
Conclusions:
- HepaRG cells exhibit high metabolic and synthetic functionality in the absence of DMSO.
- Drug metabolism is significantly enhanced in the presence of DMSO.
- A combination of CG-treated -DMSO cultures and +DMSO cultures can achieve broad hepatic functionality suitable for BAL applications.
