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Innovative Microphysiological Model Using HepatoXcell™ Primary Human Hepatocytes and Locsense Artemis

Poster
Gloved hands of young modern scientist preparing all the necessary equipment before carrying out new clinical experiment

SOT 64th Annual Meeting and ToxExpo 2025

Orlando, Florida, United States

March 20, 2025

Abstract

Background and Purpose

Lipotoxicity of the liver resulting in non-alcoholic steatohepatitis (NASH) can be caused by drugs such as amiodarone, perhexiline, and 4,4’-diethylaminoethoxyhexestrol (DH). Additionally, multiple environmental factors such as dioxin and Persistent Organic Pollutant (POP) exposure can contribute to the pathogenesis of this disease. Toxicologists assess for signs of liver damage that can result in liver diseases, such as NASH, in preclinical studies. Finally, there is a growing movement to identify how toxins can disrupt the gut microbiome and permeability and how this leakage can cause inflammation of the liver and hepatoxicity. To help reduce the burden of animal testing and to provide scientists with a model more representative of the in vivo situation, we generated an in-vitro gut liver model using intestinal epithelial cells and primary human hepatocytes. We then tested the effects of gut barrier integrity on the hepatocyte toxicity induced by lipopolysaccharide (LPS).

Methods

Caco-2 (ATCC HTB-37) cells were cultured on the transwell membranes for 21 days to form a mature intestinal barrier with tight junctions. HepatoXcell™ Pro (ATCC PCS-450-011) plateable cryopreserved primary human hepatocytes were cultured for 72 hours in the basolateral compartments with the transwells containing mature Caco-2 cell culture. The intestinal barrier was disrupted using EGTA. Intestinal barrier integrity was assessed by impedance and trans epithelial electrical resistance (TEER) measurements using the Locsense Artemis system. Cellular toxicity was induced by the addition of 2 µg/mL lipopolysaccharide (LPS) for 24 hours. Hepatotoxicity was measured by the WST-1 assay, along with measurement of hepcidin and iNOS expression.

Results

Treatment with 5 mM EGTA caused damage to the barrier integrity of the Caco-2 cell culture as determined by the TEER measurement. When assessing hepatic toxicity induced by LPS, it was found that the hepatocytes cultured with Caco-2 cells that had damaged intestinal barrier integrity had significantly lower number of viable hepatocytes compared to the hepatic culture with undamaged intestinal barrier integrity.

Conclusions

A damaged gut-liver model with disrupted intestinal barrier function was found to be more susceptible to hepatic toxicity induced by LPS. This gut-liver model system can be used to assess hepatotoxicity of different compounds that may work through damaged intestinal barrier function as an alternative to in vivo animal models.

Download the poster to learn more about the use of HepatoXcell™ as a microphysiological model.

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Presenters

Sujoy Lahiri, PhD, Lead Scientist, ATCC

Sujoy Lahiri, PhD

Lead Scientist, R&D, ATCC

Sujoy Lahiri, PhD, is an R&D scientist in ATCC. He leads the primary cell division, working on advanced cellular models using primary cells as well as expansion of ATCC’s primary cell portfolio. Dr. Lahiri has extensive knowledge in the field of toxicology and drug metabolism.

Headshot of Eline Geervliet

Eline Geervliet, PhD

Application Scientist, Locsense

At Locsense, Eline Geervliet, bridges the gap between scientific research and practical applications. There, her primary goal is to improve in vitro detection of several toxicological models, thereby reducing the necessity for in vivo testing. Eline Geervliet completed her PhD at the University of Twente, in close collaboration with RWTH Aachen, where she developed novel in vitro models to mimic different organs to investigated novel therapeutic targets. She received her Masters at the University of Twente, where she investigated pH-responsive smart polymersomes for MMP-1 delivery and treatment of liver cirrhosis.

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HepatoXcell™ by ATCC logo

Primary human hepatocytes are considered the gold standard for in vitro liver models due to their high predictive value in drug metabolism and toxicity studies. They can provide early insights into how a drug will behave in the human body, potentially reducing the risk of adverse effects in clinical trials. ATCC hepatocytes are meticulously isolated and characterized to ensure the highest quality and performance for your drug development and toxicity testing needs. Try our HepatoXcell™ primary human hepatocytes and media today!

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