Organ Model: Respiratory System

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:

Bone (Metastasized Breast Cancer)

• Multi-omics qualification of an organ-on-a-chip model of osteolytic bone metastasis

Brain

• A guided approach to establish a functional humanized Brain-on-a-Chip microfluidic model of the neurovascular system

Intestine

• Gene expression profiling reveals enhanced nutrient and drug metabolism and maturation of hiPSC-derived intestine-on-chip relative to organoids and Transwells
• Establishing the human Duodenum-Chip as a surrogate for effective human permeability: In vitro and in silico assessment

Liver

• Challenges and solutions in measuring commonly used biomarkers for drug-induced liver injury in a Liver-On-A-Chip platform

Lung

• Lung microphysiological system validates novel cell therapy for Acute Respiratory Distress Syndrome
• Revealing the impact of Pseudomonas aeruginosa quorum sensing molecule 2’-aminoacetophenone on the human bronchial-airway epithelium and pulmonary endothelium using a human airway-on-a-chip

Vasculature

• Human coronary artery tri-culture organ-chip 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 (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.

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

Authors

Naomi S. Coombes¹, Tanja Šuligoj², Rhiannon Davies¹, Tessa Prince², Lisa Luu², Conner Norris¹, Julian Hiscox², Yper Hall¹, Simon GP Funnell³, Kevin R. Bewley¹

¹UK Health Security Agency, Porton Down, Salisbury, UK; ²Institute of Infection, Veterinary and Ecological Sciences, University of Liverpool, Liverpool, UK; ³Gut Microbes and Health, Quadram Institute Bioscience, Norwich, UK

Abstract

The SARS-CoV-2 pandemic caused significant worldwide disruption to economies and healthcare systems. It is predicted that the frequency at which new pandemics occur in the future will increase due to factors such as climate change, global population increase, intensification of agriculture and closer contact with wildlife. All but one of the pathogens on the current WHO R&D emergency context priority disease list are viruses which require work to be performed at containment level 3 or 4 (BSL3 or BSL4). There is a need for physiologically relevant in vitro systems to assist pre-clinical research in preparedness for the next pandemic. For example, Disease X which by definition will be a human disease, may not infect current cell lines or animal models commonly used in virus research.

Here the authors present the results from infections with SARS-CoV-2, SARS-CoV-1 and MERS-CoV of an alveolar model using the commercially available Emulate system at BSL3. They also describe the results from antiviral assessment in this model.

Organ Model: Lung (Airway)

Application: Infectious Disease, Immunology & Inflammation

Highlights

In this study, the researchers created an Airway Lung-Chip that contains primary human airway epithelial cells (from either healthy donors or COPD patients) cultured at an air–liquid interface above a channel lined with pulmonary endothelial cells. This chip faithfully reproduces many features of the human airway, including differentiation into multiple cell lineages, mucus production, and barrier integrity. By infecting the Airway Lung-Chips with influenza virus, they could directly compare how healthy versus COPD airway cells respond to infection and drug treatments in a more physiologically relevant environment. Notably, they showed that COPD Airway Lung-Chips exhibit heightened viral replication and inflammation, mirroring the exacerbated disease states seen in patients. The Airway Lung-Chip experiments consistently showed higher viral replication and more pronounced inflammatory responses compared to static Transwell cultures, suggesting that the dynamic microenvironment on the chip better recapitulates in vivo airway physiology.

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Organ Model: Lung (airway)

Application: Immunology & Inflammation, Cancer

Highlights

The authors of this study leveraged Organ-Chips to model cystic fibrosis airways. The researchers used CRISPR/Cas9 to knock out CFTR in human bronchial epithelial cells, then grew them in Chip-S1 Organ-Chips to study how CFTR loss drives inflammation, immune cell recruitment, and epithelial invasiveness — key features of CF lung disease. Compared to wild-type controls, CFTR-deficient chips showed increased recruitment of polymorphonuclear neutrophils and greater migration of epithelial cells into the endothelial channel, reflecting a pro-inflammatory, EMT-associated phenotype. These chip-based functional assays complemented proteomic findings, linking CFTR loss to pathways involved in cancer progression and immune cell recruitment.

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