Assessment of the cytotoxic and anti-infective activity of compounds using human lung organoid models
Human and animal health In vitro/ex vivo cytotoxicity
Background of in vitro 3D organoid model development
Cell culture remains a cornerstone of preclinical drug development, particularly in infectious diseases and respiratory research. Historically, two-dimensional (2D) cell culture systems have been widely used due to their simplicity and scalability. However, these models fail to reproduce the architectural complexity, cellular heterogeneity, and physiological responses of native human tissues.
Recent advances in three-dimensional (3D) organoid technologies have enabled the development of miniaturized, physiologically relevant human tissues derived from primary cells. Lung organoids represent mini-organs generated from patient-derived epithelial cells, capable of mimicking both healthy and pathological conditions.
In particular, apical-out lung organoids reproduce the structural and functional features of airway epithelium, including differentiated cell populations such as ciliated and basal cells, functional epithelial barriers with tight junctions, and physiological responses to pathogens and environmental stressors.
These models provide a translational bridge between in vitro assays and in vivo studies, improving predictive accuracy while reducing reliance on animal models.
Objectives of the model
The primary objective of this model is to:
Evaluate the cytotoxicity profile of candidate compounds on human lung organoids
Assess anti-infective efficacy against bacterial or viral pathogens
Characterize host-pathogen interactions, including epithelial response and inflammation
Generate translational data to support preclinical decision-making
Our approach at Vibiosphen
Organoid production and culture
- Human primary bronchial epithelial cells cultured into 3D organoids within approximately 15 days
- Apical-out configuration enabling direct interaction with pathogens or compounds
- Use of well-characterized donor-derived cells, including healthy and diseased profiles
Compound testing
- Application of a range of concentrations in triplicate
- Controlled incubation at 37°C and 5% CO2
- Time-course analysis depending on study design
Infection models
Bacterial infection model
• Example: Pseudomonas aeruginosa
• Kinetics: 2 h, 4 h, 8 h, 24 h
• Readouts: CFU quantification, microscopy, cytokine profiling
Viral infection model
• Example: SARS-CoV-2
• Kinetics: 24 h, 48 h, 72 h
• Readouts: viral titration (qPCR, PFU, TCID50), cytopathic effects
Endpoints and analytical readouts
• Cell viability assays
• Structural and histological analysis
• Cytokine and chemokine profiling (e.g., IL-17, TNF-α)
• Microscopy-based phenotypic assessment
• Barrier integrity and epithelial response
Outcomes of in vitro 3D organoid models
Organoid-based models offer significant advantages compared to conventional systems:
- High physiological relevance due to the use of primary human cells
- Ability to model both healthy and pathological states
- Improved prediction of clinical efficacy and toxicity
- Reduction of late-stage drug development failures
- Compatibility with high-throughput screening approaches
- Enhanced design of subsequent in vivo studies
Additionally, these models are validated for applications in lung organoid production, viral infection studies, and bacterial infection models.
Why Choose Vibiosphen?
• Proven expertise in infectious disease preclinical research
• Advanced organoid and 3D tissue platforms
• Flexible and customized study designs adapted to sponsor requirements
• Advanced facilities ensuring reliable and reproducible results (BSL2 and BSL3)
• Strong collaborations with pharmaceutical companies, biotech firms, and academic partners
Vibiosphen combines scientific excellence with industry know-how to deliver actionable preclinical data that drive innovation in infectious disease therapeutics.
Contact Us
If you are developing new treatments or vaccines, Vibiosphen can help accelerate your research.
Contact us today to discuss your project and explore how our Pharmacokinetics models can support your development strategy. We will be pleased to facilitate your project by providing a customized study design to your project objectives.