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Hepatotoxicity and ADME services 

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Why us

Our NANOSTACKSTM-based in vitro models recapitulate the cell-cell crosstalk, fluid flow and spatial cellular arrangement typical of the in vivo environment. This way, toxicity screening on our models can yield more accurate results than the use of traditional models. We provide in vitro testing services using the in vitro model of your choice. 

Why choose our NANOSTACKSTM liver models 

Superior performance compared to other hepatic models

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NANOSTACKSTM liver models

NANOSTACKSTM-based models integrate fluid flow, mimicking the liver's mechanical environment, and incorporate various hepatic cell types in a spatially accurate arrangement, including the space of Disse. Unlike standard coculture models where proliferating cells can disrupt reproducibility, NANOSTACKSTM maintain constant cell populations, ensuring consistency. Moreover, isolating cell types on NANOSTACKSTM is straightforward, and they are compatible with assays commonly used for hepatotoxicity and ADME studies.

Hepatocytes monocultures

Hepatocyte monocultures offer consistent results, work well with lab assays and are widely used in pharmaceutical research for tasks like ADME and hepatotoxicity studies. Yet, they lack cell-cell communication with other cell types, in vivo-like spatial organization, and fluid flow typical of the liver environment, limiting their ability to replicate in vivo conditions and the regulation of hepatocyte function.

Mixed hepatic cocultures

Mixed cocultures of hepatocytes and other hepatic cells mimic in vivo cell diversity but lack representative spatial organization. Proliferating cells may dominate unpredictably, challenging reproducibility. Separating cell types for assays is difficult, limiting endpoints. The model lacks fluid flow, hindering replication of the hepatic environment.

Sandwich hepatic cocultures

Sandwich cocultures of hepatocytes and other hepatic cells replicate liver cell diversity and partial spatial distribution seen in vivo. Yet, they lack the space of Disse, featuring unrealistic cell-cell and cell-ECM contacts. Proliferating cells can dominate, reducing reproducibility, and the complex structure complicates isolating cell types for assays. Like other models, they lack fluid flow.

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Click on the options below to explore our validated solutions for hepatotoxicity and ADME studies

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NANOSTACKSTM liver monoculture model 

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NANOSTACKSTM liver triculture model

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NANOSTACKSTM liver tetraculture model

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The model is built using our proprietary NANOSTACKS™ technology

  • Layer 1: Hepatocytes compartment 
  • Cell type: Primary human hepatocytes
  • Primary human hepatocytes (PHH) are the gold standard for hepatotoxicity screening due to their physiological relevance and ability to recapitulate key liver functions, such as CYP activity and albumin production. The model can be utilized in various ways, including as a standalone model or as a control for our triculture and tetraculture models.
  • Fluid flow included

OUTPUTS

Cytotoxicity

CYP450

Albumin

Urea

Contact us for alternative endpoints.

Comprehensively validated liver monoculture model

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Liver PHH cells on NANOSTACKSTM

Representative widefield images of primary human hepatocytes (PHH) in NANOSTACKSTM. Magnification: 10X. 

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Long term model culture 

Primary human hepatocytes (PHH) grown on NANOSTACKSTM under both flow and static conditions maintained viability for 31 days of the study, with no substantial differences between static and flow conditions. Data:  mean ± SEM. N = 3 on day 2, 4, 7,11, 14, 20 and 26.

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Sustained metabolic competence

The NANOSTACKSTM model of primary hepatocytes (PHH) maintained active metabolic activity throughout the 31-day study period. However, the introduction of flow into the model resulted in significantly higher CYP3A4 activity between days 4 and 14 compared to the static model. Data: mean ± SEM, N = 3 on days 2, 4, 7, 11, 14, 20, 26, and 31.

Human-like albumin levels

Albumin production in primary human  hepatocytes reached human threshold levels (17.8 µg/million/hepatocytes) by day 4 of culture, peaking at approximately 40 µg on day 7. The model maintained above threshold levels until day 26 in both static and flow conditions, except on day 26 when albumin levels in the flow condition decreased to 8.9 µg. Data: mean ± SEM. N = 3 on days 2, 4, 7, 11, 14, 20, and 26.

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Human-like urea levels

Under static conditions, human primary hepatocytes (PHH) on NANOSTACKSTM maintained human-relevant levels of urea (>56 µg/million/hepatocytes/day) for 7 days, decreasing to 24.25 µg by day 14. Conversely, when flow was introduced into the model, the human urea level threshold was extended until day 14. Data: mean ± SEM, N = 3 on days 2, 4, 14 and 26.

Clinical translatability

The NANOSTACKSTM human primary hepatocytes (PHH) model accurately predicts hepatotoxicity of Zileuton, an FDA-classified high-DILI-concern drug, at clinically relevant concentrations following 6 days of repeated exposure, demonstrating its robust DILI prediction capability. Data: mean ± SEM. N = 3.

PHH monoculture model DILI screening standard process & timeline*

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*Dosing intervals and duration can be adjusted based on your requirements

Unique Benefits

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Human Relevance

Developed entirely using primary human cells, ensuring translational value with consistent results.

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Intercellular communication

Cell-cell crosstalk between key hepatic cells is replicated in the model, increasing its similarity to the in vivo environment.

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Inclusion of fluid flow

Fluid flow can be included in the model, modelling the natural mechanical environment of the liver.

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Differential toxicity evaluation

Toxicity can be evaluated on each individual cell type included in the model.

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Long-term studies

Cells included the model are viable up to 31 days, providing the possibility to perform long-term toxicity screenings.

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High quality cells

Our cells are obtained from trusted suppliers and consistently perform key hepatic functions.

Get in Touch

Explore how our models support your research studies

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Alternative solutions

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MODEL SHIPPING

Alternatively to performing our services within our facilities, we can also ship our validated organ models directly to you lab ready for immediate use.

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CUSTOM MODEL DEVELOPMENT

We can develop custom organ models using our NANOSTACKSTM 'Plug&Play' technology based on your requirements.

Need some help?

If you're interested in discovering how  our organ models can benefit your research, we invite you to get in touch with us. Our team is available to provide further insights and address any inquiries you may have.

Contact information

UK

Daresbury Laboratory, Sci-Tech Daresbury, Keckwick Lane Daresbury, Cheshire, WA4 4AD

+447588015987

info@revivocell.com

USA

BioLabs@NYU LANGONE, 180 Varick St, Floor 6, New York, NY 10014


info@revivocell.com

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