The HUREL® Micro Liver Advantage

HUREL® Micro Livers 2D cell culture system has proved to be exceptional for DMPK studies, metabolite ID studies, metabolite generation studies and metabolic clearance studies due to its 60% hepatocyte density. Additionally, the system has been widely published in the fields of viral liver disease modeling and liver toxicity.

This proprietary model consists of self-assembling co-cultures (SACCs) of primary hepatocytes that are cryopreserved and combined with a non-parenchymal (stromal) cell line. In this form of liver cell culture the hepatocytes spontaneously self-assemble into colonies.

The HUREL system is:

Metabolically Competent
The HUREL system is derived in part from their multi-fold greater hepatocyte number and therefore has greater cell density within the microtiter well. This is the characteristic most centrally responsible for HUREL’s delivering data of superior translational predictivity for DMPK studies.

Phenotypically Stable

Rock-solid, long-enduring phenotypic stability creates the foundation for the superior metabolic competency that distinguishes data generated on the HUREL platform from that of primary hepatocytes cultured in suspension, in monoculture, in micropatterned arrays, and in 3D spheroids.

Peer Reviewed & Validated

The world’s leading pharmaceutical companies have utilized the HUREL micro liver models in dozens of publications to date and are integral to services at many contract research organizations.

HUREL Micro Livers are offered as both a product and a service, with both options discussed below.

HUREL Services

Cytotoxicity and Hepatotoxicity Screening: The cytotoxicity and hepatotoxicity screening service makes early, high-acuity assessment of hepatotoxic risk cost-effective for smaller organizations and thereby brings new illumination to the challenge of reducing late-stage candidate attrition. This service is available in all HUREL models with an ATP readout as its main endpoint, and is ideally applied during the early lead selection stage of preclinical discovery/development.

Multi-Parameter Toxicity (HUREL Tox™): The Multi-Parameter Toxicity assay applies HUREL ’s superior metabolic competency to a panel of complementary assays, creating a multi-parametric characterization of hepatotoxic risk. HUREL Tox™ incorporates a 14-day, repeat-dose cytotoxicity study with both ATP and albumin (ELISA) readouts. Computation of time-based HUREL ratios™ and ACEA RTCA impedance signal indices illuminate potential chronic liabilities of pre-candidate NME’s.  Incubation in the absence and presence of broad CYP inhibitor aminobenzotriazole (ABT) reads on the potential for formation of reactive metabolites. Incubation in the absence and presence of bile salts provides a marker of potential cholestatic liability. Lastly, the HUREL Tox™  assay panel can be custom-configured according to the client’s particular study design.

Metabolic Clearance: The HUREL micro liver coculture system is a robust and reliable method for human in vivo clearance prediction and metabolite detection of slowly metabolized drugs. The coculture system has similar phase I and phase II enzyme activity as freshly thawed hepatocytes for at least 10 days, which enables a range of in vitro studies to predict the human in vivo situation. The system has been thoroughly validated by many companies such as AstraZeneca, as demonstrated in the following article:

Metabolite Generation and ID: HUREL micro livers produce robust metabolite yields that closely correlate to metabolites generated by parent compounds in vivo. HUREL® ‘s met-gen competency is species-specific—including monkey, rat, and dog.

Reaction Phenotyping Assay: Visikol utilizes the HUREL Human Pool™ Primary Hepatocyte Micro Liver Model, which maintains stable metabolic activities in long-term cultures (> 4 weeks). This model is more physiologically relevant and has a complete complement of drug metabolizing enzymes (CYPs and non-CYPs) and cofactors. Using HUREL Human Pool™ primary hepatocyte micro liver model, intrinsic clearance rates for parent drug depletion in the absence and the presence of CYP inhibitors are measured to determine the contribution of CYP enzymes. This information is useful to identify the specific enzymes responsible for the drug metabolism

HUREL Products

We ship ready-to-use plates in pooled human, as well as a variety of species both large and small animals in plate formats, directly to your lab’s doorstep to be used in your own workflows. To ensure products are delivered to our clients unharmed, we have developed a robust packaging method designed with viability in mind. Packages ship from our lab in Ashland, Massachusetts, and have made sure shipping is simple; simply provide the address where you would like your plates delivered and we will manage all the logistics. We can ship both domestically and internationally. To start using your plates, simply remove the cell culture plate from the protective sleeve, remove the rubber bands, remove the lid, peel off the sealing film and you are ready to go!

HUREL® Cat™
Co-culture comprised of cryopreserved primary feline hepatocytes cultured with cells of non-parenchymal, stromal type.

HUREL® Dog™
Co-culture comprised of cryopreserved primary dog hepatocytes cultured with cells of non-parenchymal, stromal type.

HUREL® Human™
Co-culture comprised of cryopreserved primary human hepatocytes cultured with cells of non-parenchymal, stromal type.

HUREL® Human Pool™
Co-culture comprised of pooled cryopreserved primary human hepatocytes cultured with cells of non-parenchymal, stromal type.

HUREL® Minipig™
Co-culture comprised of cryopreserved primary minipig hepatocytes cultured with cells of non-parenchymal, stromal type.

HUREL® Mouse™
Co-culture comprised of cryopreserved primary mouse hepatocytes cultured with cells of non-parenchymal, stromal type.

HUREL® Primate™
Co-culture comprised of cryopreserved primary primate hepatocytes cultured with cells of non-parenchymal, stromal type.

HUREL® Rabbit™
Co-culture comprised of cryopreserved primary Rabbit hepatocytes cultured with cells of non-parenchymal, stromal type.

HUREL® Rat SD™
Co-culture comprised of cryopreserved primary rat hepatocytes cultured with cells of non-parenchymal, stromal type.

HUREL® Rat WH™
Co-culture comprised of cryopreserved primary rat hepatocytes cultured with cells of non-parenchymal, stromal type.

HUREL® Zooplates™
12 different models representing 10 mammalian species. Offered as individual species cultured in microtiter plates of any standard well size or, for added speed and convenience at the bench, as ZooPlates™  —  micro livers of multiple species custom-configured on a single labware plate.

Tips for HUREL Plates

Tip #1: Acclimate the Plates in an Incubator Overnight

When you receive your HUREL Micro Livers, it is important to acclimate the plates in an incubator overnight before use in an experiment. This will ensure that the cells are at the optimal temperature and are ready for use. For same-day experiments, it is recommended to allow the cells to acclimate in an incubator for a minimum of at least 4 hours before use in an experiment.

Tip #2: Change the Plate’s Media with the Maintenance Media Every 2 Days

To maintain the health and viability of the cells, it is important to change the plate’s media with the maintenance media every 2 days. This will ensure that the cells have the nutrients and conditions they need to thrive. It is recommended to use the culture plate within 4 days of receiving.

Tip #3: Use the Recommended Incubation Volume

The recommended incubation volume for HUREL Micro Livers depends on the plate format and the number of hepatocytes per well. It is important to use the recommended volume to ensure optimal cell density and viability. The recommended volume ranges from 30-50 μL for a 384-well plate with 11,000 hepatocytes per well to 2000-2400 μL for a 6-well plate with 940,000 hepatocytes per well.

Interested in learning more HUREL Products and Services? Reach out to a member of our team to get started today.