Advanced pathophysiology mimicking lung models for accelerated drug discovery

Area of Science:

• Biotechnology
• Respiratory Medicine
• In Vitro Models

Background:

• Respiratory diseases are a leading global cause of death, with limited therapeutic options due to a lack of effective lung models.
• Current treatments for chronic lung diseases are primarily supportive, highlighting the urgent need for novel therapeutic development.

Purpose of the Study:

• To establish advanced, reliable, and reproducible in vitro lung models that mimic both healthy and diseased (COPD) lung complexity.
• To accelerate the development and high-throughput testing of new therapeutics for respiratory diseases.

Main Methods:

• Utilized five key design components: cell type, membrane structure, environmental conditions, cellular arrangement, and substrate/matrix composition.
• Implemented a quality control strategy with real-time and end-point measurements of cellular barrier function, permeability, tight junctions, tissue structure, composition, and cytokine secretion.

Main Results:

• Developed a healthy lung model with continuous tight junctions, physiological barrier function, a multi-layered epithelium, and presence of ciliated/goblet cells.
• Created a COPD model exhibiting dysfunctional barrier function, depleted ciliated cells, and goblet cell overproduction, mimicking human disease.
• Highlighted competitive advantages including macroscale for multimodal characterization, patient-derived cells for personalized medicine, extracellular matrix for cell adhesion, and microcirculation for dynamic conditions.

Conclusions:

• The developed lung models are suitable for evaluating the safety, efficacy, and superiority of new therapeutics.
• Models can assess toxicity and injury from inhaled pollutants or pathogens, and test protective therapeutics for high-risk individuals.