Cryopreserved HepaRG™ Cells
Description:
Cryopreserved HepaRG™ Cells
Qty/Pk:
1 mL
Background Information:
Hepatocytes are an important and fundamental tool for the study of both a drugs’ metabolism and it’s toxicity. Traditionally hepatocytes have been sourced from from livers not accepted for transplant or from the resected margin of liver carcinoma patients. However, this supply of fresh hepatocytes is unpredictable, the material is often of poor quality, subject to genetic and environmental variability and increasingly costly.
Currently customers are forced to utilize less than ideal tissue sources, including recombinant enzymes expressed in non-mammalian cells, rat hepatocytes, human enzymes and transporters expressed in non-hepatocyte recombinant cell lines, and cryopreserved human hepatocytes. All of these solutions lose some or most of the functional activities of hepatocytes freshly isolated from a healthy human donor.
HepaRG™ cells are terminally differentiated hepatocyte cells that reproducibly express the activities of transporters and drug metabolizing enzymes and facilitate studies of uptake, metabolism, and disposition of drug candidates.
They respond and function like primary human hepatocytes across a range of applications.
They do not require daily medium changes, are reproducible and can be stored until required
Can be used across different types of studies at a lower overall cost than human primary hepatocytes
Currently customers are forced to utilize less than ideal tissue sources, including recombinant enzymes expressed in non-mammalian cells, rat hepatocytes, human enzymes and transporters expressed in non-hepatocyte recombinant cell lines, and cryopreserved human hepatocytes. All of these solutions lose some or most of the functional activities of hepatocytes freshly isolated from a healthy human donor.
HepaRG™ cells are terminally differentiated hepatocyte cells that reproducibly express the activities of transporters and drug metabolizing enzymes and facilitate studies of uptake, metabolism, and disposition of drug candidates.
They respond and function like primary human hepatocytes across a range of applications.
They do not require daily medium changes, are reproducible and can be stored until required
Can be used across different types of studies at a lower overall cost than human primary hepatocytes
Applications:
HepaRG™ cells are terminally differentiated human hepatocellular carcinoma cells that reproducibly express the activities of transporters and drug metabolizing enzymes.
Key Applications:
- Cell Based Assays
- Drug Transport
- High Content Analysis
- Toxicology Assays
Application Notes:
The similarity of HepaRG™ to human hepatocytes is well described in journal papers:
“HepaRG activities comparable to those usually found in primary human hepatocyte cultures.” (1)
“hepatocytic markers and liver specific proteins such as albumin are expressed at levels similar to those found in normal liver. Iron storage and metabolism typical of human hepatocytes are intact with HepaRG cells.” (2)
“The (data) generated from the HepaRG cells (were) in excellent agreement with those generated in human hepatocytes” (3)
“The high percentage of translationally controlled probe sets (in HepaRG) is in agreement with the … hepatocyte” (2)
“… the extensive inter-individual variation … renders it difficult to compare data with human hepatocytes … these drawbacks appear to be … overcome with HepaRG cells.” (1)
Metabolic activity of HepaRG™ is comparable to that of human hepatocytes and is reproducible and maintained for multiple weeks:
“ For (CYP3A4) HepaRG activities ranged between 600 and 800 pmol/min/mg during the four-week period, comparable with those usually found in primary human hepatocyte cultures” (1)
“Activities of CYP3A4 and CYP1A2 were found to be relatively stable over the four-week period” (4)
“Our results clearly show that 1099 genes were affected in common in 6 independent experiments using HepaRG in two different laboratories” (1)
HepaRG™ have demonstrated utility for in-vitro assessment of CYP inhibition:
“CYP activities in HepaRG cells are inhibited by diagnostic inhibitors to the same extent as in primary hepatocytes” (5)
HepaRG™ are useful for in-vitro determinations of acute toxicity, mitochondrial damage, metabolite-dependent toxicity, genotoxicity and chronic toxicity risk:
“Our data confirmed that (HepaRG) are metabolically competent and activate different classes of promutagens into reactive metabolites.” (6)
HepaRG™ demonstrate uptake and efflux transporter expression and responses that closely resemble those of human hepatocytes:
“HepaRG were found to display a pattern of transporter expression close to that found in primary human hepatocytes.” (7)
“The fact that HepaRG cells exhibit functional activity of both sinusoidal and canalicular drug transporters is important.” (7)
HepRG™ respond to prototypical inducers including those that activate CAR such as CITCO, which is dependent solely on the CAR pathway, in a fashion similar to the responses of primary human hepatocytes, but HepaRG™can be used for much longer periods than PHH:
“Across nine inducers, the R2 of fold induction of HepRG compared to the mean induction with three lots of primary hepatocytes was 0.94” (8)
References
1. Lambert et al. Toxicology in Vitro. (2009) 10.1016.
2. Parent et al. Genome Biology. 2008, 9:R19.
3. McGinnity et al. Drug Metabolism and Disposition. 37:1259-1268, 2009.
4. Josse et al. Drug Metabolism and Disposition. 36:1111-1118, 2008.
5. Turpeinen et al. Toxicology in Vitro. (2009) 10.1016. 2009.03.008.
6. Le Hegarat et al. The human hepatoma HepaRG cells: a suitable in-vitro model to assess the genotoxic potential of bio activated chemicals. European Environmental Mutagen Society, 2008.
7. LeVee et al. European Journal of Pharmaceutical Sciences. 28(2006) 109-117.
8. Kanebratt et al. Drug Metabolism and Disposition. 36:137-145, 2008.
“HepaRG activities comparable to those usually found in primary human hepatocyte cultures.” (1)
“hepatocytic markers and liver specific proteins such as albumin are expressed at levels similar to those found in normal liver. Iron storage and metabolism typical of human hepatocytes are intact with HepaRG cells.” (2)
“The (data) generated from the HepaRG cells (were) in excellent agreement with those generated in human hepatocytes” (3)
“The high percentage of translationally controlled probe sets (in HepaRG) is in agreement with the … hepatocyte” (2)
“… the extensive inter-individual variation … renders it difficult to compare data with human hepatocytes … these drawbacks appear to be … overcome with HepaRG cells.” (1)
Metabolic activity of HepaRG™ is comparable to that of human hepatocytes and is reproducible and maintained for multiple weeks:
“ For (CYP3A4) HepaRG activities ranged between 600 and 800 pmol/min/mg during the four-week period, comparable with those usually found in primary human hepatocyte cultures” (1)
“Activities of CYP3A4 and CYP1A2 were found to be relatively stable over the four-week period” (4)
“Our results clearly show that 1099 genes were affected in common in 6 independent experiments using HepaRG in two different laboratories” (1)
HepaRG™ have demonstrated utility for in-vitro assessment of CYP inhibition:
“CYP activities in HepaRG cells are inhibited by diagnostic inhibitors to the same extent as in primary hepatocytes” (5)
HepaRG™ are useful for in-vitro determinations of acute toxicity, mitochondrial damage, metabolite-dependent toxicity, genotoxicity and chronic toxicity risk:
“Our data confirmed that (HepaRG) are metabolically competent and activate different classes of promutagens into reactive metabolites.” (6)
HepaRG™ demonstrate uptake and efflux transporter expression and responses that closely resemble those of human hepatocytes:
“HepaRG were found to display a pattern of transporter expression close to that found in primary human hepatocytes.” (7)
“The fact that HepaRG cells exhibit functional activity of both sinusoidal and canalicular drug transporters is important.” (7)
HepRG™ respond to prototypical inducers including those that activate CAR such as CITCO, which is dependent solely on the CAR pathway, in a fashion similar to the responses of primary human hepatocytes, but HepaRG™can be used for much longer periods than PHH:
“Across nine inducers, the R2 of fold induction of HepRG compared to the mean induction with three lots of primary hepatocytes was 0.94” (8)
References
1. Lambert et al. Toxicology in Vitro. (2009) 10.1016.
2. Parent et al. Genome Biology. 2008, 9:R19.
3. McGinnity et al. Drug Metabolism and Disposition. 37:1259-1268, 2009.
4. Josse et al. Drug Metabolism and Disposition. 36:1111-1118, 2008.
5. Turpeinen et al. Toxicology in Vitro. (2009) 10.1016. 2009.03.008.
6. Le Hegarat et al. The human hepatoma HepaRG cells: a suitable in-vitro model to assess the genotoxic potential of bio activated chemicals. European Environmental Mutagen Society, 2008.
7. LeVee et al. European Journal of Pharmaceutical Sciences. 28(2006) 109-117.
8. Kanebratt et al. Drug Metabolism and Disposition. 36:137-145, 2008.
Usage Statement:
Unless otherwise stated in our catalog or other company documentation accompanying the product(s), our products are intended for research use only and are not to be used for any other purpose, which includes but is not limited to, unauthorized commercial uses, in vitro diagnostic uses, ex vivo or in vivo therapeutic uses or any type of consumption or application to humans or animals.
Species:
Human
Quality Assurance:
Mycoplasma Testing:
The cell line has been screened to confirm the absence of Mycoplasma species
The cell line has been screened to confirm the absence of Mycoplasma species
Components:
Pack contains 1vials of mycoplasma-free cells, 1 ml per vial (>8 x 106 cells)
Storage Conditions:
Store in Liquid Nitrogen
Packaging:
Vial
Long Description:
Cryopreserved, terminally differentiated hepatic cells derived from a human liver progenitor cell line that retains many characteristics of primary hepatocytes
Product Name:
Cryopreserved HepaRG™ Cells
Materials Required but Not Delivered:
HepaRG Thawing/Plating Medium Supplement (Cat.No.: MMADD671)
HepaRG Culture Medium Supplement (Cat.No.: MMADD621)
HepaRG Tox Medium Supplement (Cat.No.: MMADD631)
HepaRG Induction Medium Supplement (Cat.No.: MMADD641)
HepaRG Serum Free Induction Medium Supplement (Cat.No.: MMADD651)
HepaRG Culture Medium Supplement (Cat.No.: MMADD621)
HepaRG Tox Medium Supplement (Cat.No.: MMADD631)
HepaRG Induction Medium Supplement (Cat.No.: MMADD641)
HepaRG Serum Free Induction Medium Supplement (Cat.No.: MMADD651)