A prognostic molecular signature of hepatic steatosis is spatially heterogeneous and dynamic in human liver

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.

Products Used In This Publication

Chip-R1 Rigid Chip: Improved Precision in ADME-Tox Testing

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.

Liver Toxicology White Paper: Setting a New Standard in Drug Safety Testing

Discover how the Liver-Chip S1 is transforming drug development and toxicology prediction. This white paper highlights key findings from our 2022 Communications Medicine study, where the Liver-Chip achieved 87% sensitivity and 100% specificity in detecting drug-induced liver injury across 870 chips.

What’s inside:

  • How the Liver-Chip S1 outperforms traditional models by delivering human-relevant insights into drug safety.
  • The potential $3B+ annual productivity impact of integrating the Liver-Chip S1 into R&D workflows.
  • Regulatory milestones, including Liver-Chip S1 acceptance into the FDA ISTAND program.
  • Advancing drug testing precision with the Liver-Chip R1, which addresses non-specific binding.

Explore the next generation of preclinical safety testing. Download the white paper now to see how Emulate Organ-on-a-Chip technology is reshaping toxicology prediction and accelerating safer therapeutics to market.

Liver-Chip R1 Application Note

The Chip-R1 Rigid Chip minimizes drug absorption while maintaining the essential architecture of Chip-S1. This enables researchers to build biologically complex Organ-Chip models for tissues that do not require stretch (e.g., liver, kidney, brain, and lung airway).

Here, we describe the development of the Chip-R1 Rigid Chip and the Liver-Chip R1 organ model, including data from an equivalency study that demonstrates its utility in modeling the liver and predicting drug hepatotoxicity.

  • The Chip-R1™ Rigid Chip has the same two-channel configuration as the Chip-S1® Stretchable Chip, with several updates, including reduced drug absorption.
  • The Liver-Chip R1 demonstrates robust liver functionality, as indicated by morphology, marker expression, albumin production, and drug metabolism.
  • The Liver-Chip R1 displays increased sensitivity to detecting the drug-induced liver injury risk of small-molecule drugs with absorption liability in PDMS.
  • The Chip-R1 exhibits reduced absorption of a range of small molecules with diverse physicochemical properties.

Liver-Chip R1 BioKit Data Sheet

The Liver-Chip R1 BioKit contains all the components needed to build a Liver-Chip using the Chip-R1® Rigid Chip. Designed to minimize drug absorption and enhance biological modeling by using low-drug-absorbing materials, this model is particularly well-suited for applications in which drug absorption is a concern, including human-relevant assessments of drug toxicology, efficacy, and ADME profiles​​.

Human quad liver-on-chip system as a tool toward bridging the gap between animals and humans regarding toxicology and pharmacology of a cannabidiol-rich cannabis extract

Organ Model: Liver

Application: Toxicology

How Organ-Chips Were Used: The Liver-Chip S1 Quad-Culture was used to investigate cannabidiol-rich cannabis extracts-induced hepatotoxicity and pharmacological properties demonstrated in animal models. The users found found that while therapeutic doses were generally safe, higher concentrations disrupted antioxidant pathways and triggered mild liver injury. 

Products Used In This Publication

Organ chips with integrated multifunctional sensors enable continuous metabolic monitoring at controlled oxygen levels

Organ Model: Small Intestine & Liver

Application: Organ-on-a-Chip Technology

Abstract: Despite remarkable advances in Organ-on-a-chip (Organ Chip) microfluidic culture technology, recreating tissue-relevant physiological conditions, such as the region-specific oxygen concentrations, remains a formidable technical challenge, and analysis of tissue functions is commonly carried out using one analytical technique at a time. Here, we describe two-channel Organ Chip microfluidic devices fabricated from polydimethylsiloxane and gas impermeable polycarbonate materials that are integrated with multiple sensors, mounted on a printed circuit board and operated using a commercially available Organ Chip culture instrument. The novelty of this system is that it enables the recreation of physiologically relevant tissue-tissue interfaces and oxygen tension as well as non-invasive continuous measurement of transepithelial electrical resistance, oxygen concentration and pH, combined with simultaneous analysis of cellular metabolic activity (ATP/ADP ratio), cell morphology, and tissue phenotype. We demonstrate the reliable and reproducible functionality of this system in living human Gut and Liver Chip cultures. Changes in tissue barrier function and oxygen tension along with their functional and metabolic responses to chemical stimuli (e.g., calcium chelation, oligomycin) were continuously and noninvasively monitored on-chip for up to 23 days. A physiologically relevant microaerobic microenvironment that supports co-culture of human intestinal cells with living Lactococcus lactis bacteria also was demonstrated in the Gut Chip. The integration of multi-functional sensors into Organ Chips provides a robust and scalable platform for the simultaneous, continuous, and non-invasive monitoring of multiple physiological functions that can significantly enhance the comprehensive and reliable evaluation of engineered tissues in Organ Chip models in basic research, preclinical modeling, and drug development.

Developing an RNA Signature for Radiation Injury Using a Human Liver-on-a-Chip Model

Organ Model: Liver

Application: Toxicology

How Organ-Chips Were Used: Here, users demonstrated the potential utility of a human Liver-Chip to model organ-specific radiation injury, providing a platform for the development of radiation medical countermeasure and for biomarker validation. Users also identified biomarkers of RILI and defined cell-specific targets for potential radiation mitigation therapies.

Products Used In This Publication

Evaluating the Hepatotoxicity of Cannabidiol, Cannabinol, Cannabichromene and Cannabigerol Using a Human Quad-Culture Liver-Chip

Abstract

As the popularity of hemp-derived products grows, understanding the prospective hepatotoxicity of cannabinoids becomes crucial for personal safety. Despite conflicting evidence from limited human clinical studies, a safety gap persists, and no standard threshold has been established for these various cannabinoid-containing products. Furthermore, the hepatotoxicity potential of other cannabinoids like Cannabinol (CBN), Cannabichromene (CBC), and Cannabigerol (CBG) remains largely unexplored.

The current study was designed to address some of these gaps by utilizing microphysiological systems (MPS), such as the Emulate Quad-Culture Liver-Chip, which adhere to IQ MPS consortia guidelines, as an alternative to animal testing. Here, pressure-driven flow for compound delivery was used with primary human cells in an in vivo-like arrangement, separated by a semi-porous membrane to allow for crosstalk between the hepatocytes and nonparenchymal cells (NPCs). Hepatotoxicity was compared among CBD, CBN, CBC, and CBG, in parallel with the known hepatotoxic compound acetaminophen (APAP), in a three-point concentration response evaluation (0.24, 3, or 4.7 µM). The assessment encompassed morphological effects, hepatocyte function, and potential mechanisms of action over a 7-day continuous dosing period. These evaluations included live imaging for mitochondrial dysfunction, total reactive oxygen species (ROS), and inflammatory cytokines derived from effluent-based sampling in the Emulate platform. 

Morphological analysis revealed 3 or 4.7 µM CBD impacting hepatocytes by Day 7, while CBG exhibited no visible changes compared to the control. Endpoints evaluating hepatocyte function and viability indicated that LDH release increased only with 4.7 µM CBD, CBN, and CBC. CBD, CBN, and CBG did not significantly affect albumin, ALT, or AST, while 4.7 µM CBC significantly decreased albumin production. Inflammatory cytokines increased at high concentrations of CBD, CBC, and CBG. ROS and mitochondrial function displayed different responses among the cannabinoids affecting the NPCs more versus the hepatocytes. Up until now, the majority of what is known regarding these compounds is mostly murine-based. Hence, this study was an effort to leverage the use of advanced, human-relevant MPS to carefully assess and compare the hepatotoxicity of CBD and other cannabinoids, shedding light on their safety in foods and health products.

Organ-on-a-chip for studying immune cell adhesion to liver sinusoidal endothelial cells: the potential for testing immunotherapies and cell therapy trafficking

Organ Model: Liver

Application: Immunology & Inflammation

Abstract: Immunotherapy has changed the landscape of treatment options for patients with hepatocellular cancer. Checkpoint inhibitors are now standard of care for patients with advanced tumours, yet the majority remain resistant to this therapy and urgent approaches are needed to boost the efficacy of these agents. Targeting the liver endothelial cells, as the orchestrators of immune cell recruitment, within the tumour microenvironment of this highly vascular cancer could potentially boost immune cell infiltration. We demonstrate the successful culture of primary human liver endothelial cells in organ-on-a-chip technology followed by perfusion of peripheral blood mononuclear cells. We confirm, with confocal and multiphoton imaging, the capture and adhesion of immune cells in response to pro-inflammatory cytokines in this model. This multicellular platform sets the foundation for testing the efficacy of new therapies in promoting leukocyte infiltration across liver endothelium as well as a model for testing cell therapy, such as chimeric antigen receptor (CAR)-T cell, capture and migration across human liver endothelium.