Organ Model: Liver

With over 130 peer-reviewed publications across 30+ organ models, Emulate Organ-Chips are empowering researchers to make game-changing scientific breakthroughs! Download this digest to easily explore all publications related to your field of research, or to just learn more about how the technology itself is developing.

New this quarter:

Brain

• Modeling neurovascular dysfunction in Alzheimer’s disease using an isogenic brain-chip model

Lung

• Mechanical strain exacerbates Pseudomonas infection in an organoid-based pneumonia-on-a-chip model

Mouth

• A preliminary model of an oral dysplastic lesion on a chip

Vasculature

• Human coronary artery organ-chip with circulating immune cells recapitulates anti-inflammatory effect of pulsatile wall strain

Organ Model: Liver

Application: Toxicology

Highlights

The FDA used the Emulate Liver-Chip S1 to culture primary human hepatocytes and non-parenchymal liver cells under continuous perfusion, enabling extended drug exposure and collection of effluent for biomarker analysis. By identifying optimized ELISA- and chemistry-based methods, the study established standardized, reproducible approaches for measuring translational liver injury biomarkers in Organ-Chips, supporting their use in predictive toxicology and regulatory science.

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Synopsis

Animal models have served as the default standard in preclinical research for decades, but their limited predictive value for human outcomes continues to slow drug development and contribute to high attrition rates. Recent regulatory milestones—including the FDA’s roadmap to reduce animal use, the NIH’s prioritization of human-relevant models, and Emulate’s own Liver-Chip S1 acceptance into the FDA ISTAND program—signal a decisive shift toward New Approach Methodologies (NAMs).

In this webinar, hosted in conjunction with the Physician’s Committee for Responsible Medicine, Emulate’s Dr. Daniel Levner, Chief Technology Officer, shares how the FDA’s ISTAND qualification of the Liver-Chip S1 represents a pivotal step for regulatory recognition and broader adoption of Organ-on-a-Chip technology. Attendees will gain insight into how this breakthrough aligns with global initiatives to reduce animal testing, the scientific validation underpinning the platform, and practical strategies for integrating Liver-Chip data into regulatory submissions.

Key learning objectives

• Identify strategies for incorporating Liver-Chip data into IND submissions to increase confidence, improve predictability, and accelerate decision-making.
• Understand what FDA ISTAND acceptance means for the regulatory qualification of Organ-on-a-Chip technology and its impact on drug development.
• Learn how Emulate’s Liver-Chip S1 is poised to meet FDA expectations for context of use, building on strong scientific evidence and cross-industry collaboration.
• Explore the FDA’s roadmap to reduce animal usage and how Organ-on-a-Chip technology can future-proof your pipeline against evolving regulatory standards.

This recording was originally presented on September 10, 2025.

Organ Model: Liver

Application: Toxicology

Highlights

Researchers from AbbVie built rat and dog quad-culture Liver-Chips (hepatocytes + sinusoidal endothelial, Kupffer, and stellate cells) under physiological flow, validated one week of experimental window stability (monitoring albumin, LDH/AST, CYPs/FMO), and then dosed ABT-288. The chips reproduced in vivo, species-specific metabolism: dog chips showed much higher FMO-mediated N-oxide formation and modestly greater toxicity signals (↓albumin, ↑ALT/AST/LDH) than rat—differences that were not seen in liver microsomes or 2D hepatocytes.

Significance: animal-cell MPS models can capture species differences in metabolism-driven hepatotoxicity that conventional in vitro systems miss, providing a translational bridge that both builds confidence in human MPS readouts and can help interpret preclinical safety signals (potentially reducing animal use and de-risking First in Human decisions).

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Organ Model: Liver

Application: Toxicology

Highlights

In this study, researchers used the Emulate Quad-Culture Liver-Chip to evaluate the hepatotoxicity of four phytocannabinoids—CBD, CBN, CBC, and CBG—by continuously dosing chips for 7 days and assessing markers of liver injury. The Liver-Chip revealed compound-specific toxicity profiles, with CBC showing the most pronounced hepatotoxic effects, and provided mechanistic insights into oxidative stress and mitochondrial dysfunction in both hepatocytes and non-parenchymal cells. These findings highlight the Liver-Chip as a human-relevant alternative for liver toxicity screening of cannabinoids.

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Originally presented at the MPS World Summit 2025 Annual Meeting in Brussels, Belgium.

Authors

Randy S. Daughters¹*, Anthony R. Heng¹, Adriana Cespedes¹, Max Winkelman¹, Sushma Jadalannagari¹, Taehee Lee¹, Gabrielle Fortes¹, Jake Chaff¹, Josiah Sliz¹, Lorna Ewart¹

¹ Emulate, Inc., 27 Drydock Avenue, Boston, MA, 02210, USA

Abstract

Emulate’s new Chip-R1™ Rigid Chip is a minimally drug-absorbing Organ-Chip consumable designed for improved in vitro toxicology. It incorporates minimally drug absorbing thermoplastics along with a new porous, cell culture-treated membrane that reduce small lipophilic drug absorption. Validated with a quad culture liver model consisting of human primary hepatocytes, liver sinusoidal endothelial cells, Kupffer cells, and stellate cells, Chip-R1 supports physiological features of the liver, including albumin production and small molecule metabolism. Its reduced drug absorption enhances reproducibility and sensitivity in detecting toxicity versus PDMS-based chips. This significant improvement enables more accurate prediction of small molecule toxicity and metabolism in a human-relevant liver model, advancing drug development workflows.

Organ Model: Liver

Application: Toxicology

Highlights

Researchers used the Emulate Liver-Chip S1 Quad-Culture BioKit containing primary human hepatocytes, endothelial cells, stellate cells, and Kupffer cells to model radiation-induced liver disease (RILD). Radiation exposure on the chip reproduced key features of RILD—including DNA damage, cellular senescence, metabolic and endothelial dysfunction, inflammation, and stellate cell activation—and enabled discovery of molecular pathways involved. The chip was further used to test N-acetylcysteine amide (NACA), which reduced radiation-associated damage and supported identification of potential biomarkers for radiation response and treatment efficacy.

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Article Type: Perspective

Organ Models: Liver

Application: Toxicology

Abstract: Predicting which drugs might have the potential to cause drug-induced liver injury (DILI) is highly complex and the current methods, 2D cell-based models and animal tests, are not sensitive enough to prevent some costly failures in clinical trials or to avoid all patient safety concerns for DILI post-market. Animal-based methods are hampered by important species differences in metabolism and adaptive immunity compared to humans and the standard 2D in vitro approaches have limited metabolic functionality and complexity. On 24 April 2023 the Alliance for Human Relevant Science hosted a workshop at the Royal Society, London entitled Drug-Induced Liver Injury (DILI): Can Human-Focused Testing Improve Clinical Translation? The conclusion was that complex in vitro models (CIVMs) provide a significant step forward in the safety testing paradigm. This perspective article, written by the participants, builds on those discussions to provide a ‘state of play’ on liver CIVMs with recommendations for how to encourage their greater uptake by the pharmaceutical industry.

Organ Model: Liver

Application: Inflammation & Disease Modeling

How Organ-Chips Were Used: The Liver-Chip S1 Quad Culture was used to model hepatic steatosis and validate proteomic and transcriptomic targets identified in human cohorts.

Key highlights:

• Early stage MASLD was mimicked on Liver-Chips by treating both channels with a combination of fatty acids (oleic acid and palmitic acid) for 5 consecutive days.
• The Liver-Chip recapitulated key features of hepatic steatosis, including lipid accumulation and transcriptional changes in response to fatty acid treatment.
• The protein secretion patterns from hepatocytes and non-parenchymal cells in the Liver-Chips were consistent with the proteomic findings in human populations.
• The model demonstrated its utility for studying dynamic cellular responses to steatosis and identifying cell-specific biomarkers relevant for MASLD.

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Discover a new standard in Organ-on-a-Chip technology with the Emulate Chip-R1™ Rigid Chip. This new Organ-Chip consumable is designed to minimize drug absorption for enhanced precision in drug toxicology, ADME, and efficacy studies. The Chip-R1 maintains the two-channel architecture of the Chip-S1^® Stretchable Chip while incorporating several enhancements, including low-absorbing rigid materials, increased maximum shear stress in the vascular channel, a tissue-culture treated membrane for streamlined workflows, and a reduced chip membrane pore diameter. 

Watch our expert speakers as they dive into the advanced features of the Chip-R1 and share data from our Liver-Chip R1 Application Note, demonstrating how this consumable can be used to model the liver sinusoid and improve prediction of drug-induced liver injury (DILI). 

In this webinar, you will: 

• Discover the advanced features of the Chip-R1, including its low-absorbing materials, pre-activated tissue culture membrane, and increased maximum vascular channel shear force. 
• See how low-drug-absorbing materials reduce compound loss, enabling more precise toxicity and efficacy assessments for lipophilic small molecules. 
• Explore the Liver-Chip R1’s robust liver functionality, including albumin production, metabolic activity, and immunofluorescence imaging of the four primary cell types of the human liver sinusoid. 
• Learn how to leverage the Liver-Chip R1 for improved DILI detection, with comparative data highlighting the advantages of Liver-Chip R1 over Liver-Chip S1.