Organ Model: Respiratory System

Synopsis

Organ-on-a-Chip technology is emerging as a powerful New Approach Methodology (NAM) for drug development, driven by the need for more human-relevant and scalable experimental models. As these systems move toward broader adoption, a key challenge remains: generating consistent, interpretable data that supports confident experimental and translational decision-making.

This webinar examines how imaging and AI-driven analysis workflows enable Organ-Chip studies to scale from innovation to routine application. Speakers begin with an overview of Organ-on-a-Chip technology and its role in addressing translational gaps in drug discovery, highlighting how Liver-Chips are being evaluated in collaboration with regulatory agencies for better prediction of drug-induced liver injury.

The session then explores how the newly released AVA™ Emulation System enables scalable Organ-Chip experimentation through an integrated system for incubation, microfluidic delivery, and routine imaging. Paired with AI-driven analysis, brightfield image data can be used to automate quality control by monitoring chip health, morphology, and assay performance over time across large studies.

To complete the workflow, post-study high-resolution imaging is applied to evaluate more complex biological markers, including toxicology-relevant endpoints and drug uptake. These datasets are paired with advanced analysis techniques that translate imaging data into quantitative, biologically meaningful insights.

Attendees will gain a practical understanding of how unified imaging and analysis strategies—spanning routine QC through advanced interrogation—support scalability, reproducibility, and alignment with evolving regulatory expectations for Organ-Chips and other NAM-based drug development.

Organ Model: Lung

Applications: Immunology & Inflammation

Highlights

This study developed a more realistic in vitro model of lung transplant cold storage ischemia/reperfusion injury (CS-IRI) using a lung alveolus-on-a-chip system. Human primary alveolar epithelial cells and human lung microvascular endothelial cells were cultured under 3D microfluidic air-liquid interface conditions with physiological flow and stretch. Chips were perfused with Perfadex and stored at 4°C for 6 h, then reperfused for 24 h at 37°C to simulate CS-IRI. Compared with control chips, CS-IRI caused loss of barrier function, increased inflammatory chemokines and adhesion molecules, and significant changes in 42 epithelial and 49 endothelial cell genes (P < 0.01). This model may improve understanding of CS-IRI after lung transplantation.

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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: Lung

Applications: Immunology & Inflammation, Cell Therapy

Highlights

This publication establishes a novel Lung-Chip ARDS model for mechanistic and translational evaluation of cell therapies in human-relevant lung tissue. The ARDS model was created by co-culturing NHBE bronchial epithelial cells and HUVEC endothelial cells under flow, inducing injury with LPS in the epithelial channel, and then delivering either primed MSCs or dexamethasone through the vascular channel to compare their effects. The study shows that primed MSCs not only restore endothelial barrier function to near-control levels but also uniquely activate pro-angiogenic pathways and tip-like endothelial programs without signs of uncontrolled proliferation, suggesting they may offer a safer, regenerative alternative to dexamethasone.

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Organ Model: Lung

Applications: Infectious Disease, Immunology & Inflammation

Highlights

This study demonstrates how an organoid-based Lung-on-a-Chip model can be used to investigate ventilator-associated pneumonia (VAP) and the impact of mechanical forces on disease severity. Using the Emulate Alveolus Lung-Chip, researchers recreated key features of the human alveolar microenvironment to evaluate epithelial differentiation, barrier function, and susceptibility to Pseudomonas aeruginosa infection under physiological and injurious stretch conditions.

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Organ Model: Lung (Alveolus)

Application: Infectious Disease

Highlights

In this study, researchers used a human Alveolus Lung-Chip to test CRISPR-Cas13 RNA therapeutics targeting conserved regions of the influenza A virus genome. The chip model showed that these crRNAs potently suppressed viral replication and also reduced inflammatory cytokine release and immune cell recruitment, effects not easily captured in animal models. Transcriptomic analyses revealed minimal off-target activity, indicating strong specificity in human primary lung tissue. These findings highlight Organ-Chips as a valuable preclinical platform for evaluating both efficacy and safety of CRISPR-based antiviral therapies.

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Organ Model: Lung (airway)

Application: Methodology development

Highlights

The authors developed new methods to process and analyze Emulate Organ-Chips by trimming and paraffin-embedding Chip-S1 consumables, which enabled routine histology, immunohistochemistry, and in situ hybridization on chip cross-sections. They also applied electron microscopy workflows to assess ultrastructural features, allowing identification of cell types and organelles and localization of marker proteins. Using these approaches, they compared Airway Lung-Chips and Colon Intestine-Chips to other culture formats, showing how chips influenced differentiation trajectories and cellular composition relative to primary tissue.

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Organ Model: Lung (Airway)

Application: ADME

Highlights

In pursuit of a more reliable method for predicting the permeability of inhaled compounds during the development of new and generic drugs, the authors in this study used a small airway Lung-Chip to recapitulate the pulmonary air-liquid interface (ALI) with primary epithelial and vascular endothelial cell layers. This study showed that the small airway Lung-Chip recapitulated relevant cell types and many morphological features in the lung. The apparent permeabilities measured indicated that albuterol sulfate and formoterol fumarate would be categorized as highly permeable, while olodaterol HCl would be categorized as a low permeable drug.

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Organ Model: Lung (Airway)

Application: Infectious Disease

Highlights

Researchers used a human Airway Lung-Chip—adjacent channels lined with primary bronchial epithelium (NHBE) and pulmonary microvascular endothelium (HPMEC) under continuous flow—to expose both tissues to the P. aeruginosa quorum-sensing metabolite 2-aminoacetophenone (20 µM, 12 h) and perform RNA-seq to map cell–cell crosstalk. The Airway Lung-Chip provided a human-relevant, dynamic model that uncovered how a single bacterial QS molecule differentially reprograms airway epithelial and endothelial biology, implicating pathways and disease biomarkers that could guide therapeutic targeting.

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

Authors

Bárbara F. Fonseca¹, Jérôme Wong-Ng¹, Michael Connor², Héloïse Mary¹, Min Hee Kim¹, Rémy Yim¹, Lisa A. Chakrabarti³, Samy Gobaa¹

¹Institut Pasteur, Université Paris Cité, Biomaterials and Microfluidics core facility, C2RT, Paris, France. ²Institut Pasteur, Université Paris Cité, Chromatin and Infection Laboratory, Paris, France. ³Institut Pasteur, Université Paris Cité, Control of Chronic Viral Infections Group, Virus and Immunity Unit, Paris, France.

Abstract

The development of complex in vitro models, such as organoids, gastruloids and organ-on-chips systems, allow a better understanding of human biological processes that are otherwise difficult to address with classical in vitro 2D culture and/or with animal models. Elucidating how pathogens invade human cells by evading the immune system and how this could be modulated by the host microbiota has been greatly facilitated by the advancement of 3D cell culture techniques. Our Team is working on establishing unique advanced microphysiological systems that can mimic the interaction between human epithelial barriers with the surrounding tissues, such as blood vessels, mesenchyme and immune cells. We relay both on the use of organoids derived from human tissues and microfluidic chips.