Researchers are refining methods to study lung disease using advanced laboratory models that more closely mimic the human airway. These models, known as air-liquid interface (ALI) systems, are proving valuable for understanding how inhaled substances affect the lungs and for testing potential therapies.
The Challenge of Modeling the Airway
The human airway is a complex environment. It’s not simply a tube for air to pass through; it’s a dynamic interface between the air we breathe and the delicate tissues of the lung. This interface is crucial for functions like gas exchange, mucus clearance, and immune defense. Traditional cell cultures, where cells are grown submerged in liquid, don’t accurately replicate the conditions found in a living airway. This limitation hinders research into respiratory diseases and the development of effective treatments.
Air-Liquid Interface: A More Realistic Approach
ALI culture systems address this challenge by growing cells at the boundary between air and liquid. This allows the cells to develop a structure and function more similar to those found in the body. As detailed in research published in , cells grown at the ALI are more representative of in vivo lung cells compared to submerged cultures. Here’s because the ALI mimics the exposure to air and the formation of a mucus layer, both critical aspects of airway physiology.
Novel Advances in ALI Modeling
Recent advancements are further enhancing the realism of ALI models. A study highlighted the development of a three-dimensional (3D) airway ‘organ tissue equivalent’ (OTE) model incorporating several key features. These include native pulmonary fibroblasts – cells that provide structural support – solubilized lung extracellular matrix (ECM) proteins, and a hydrogel substrate with adjustable stiffness and porosity. The ECM provides biochemical and structural support to the cells, while the hydrogel allows for control over the physical environment.
Researchers found that cultures containing both solubilized lung ECM and pulmonary fibroblasts within the hydrogel substrate developed well-differentiated ALI cultures. These cultures maintained a barrier function and expressed markers indicating the presence of mature epithelial cells, including goblet, club, and ciliated cells – all essential components of a healthy airway. Importantly, adjusting the stiffness of the hydrogel didn’t negatively impact cell differentiation, suggesting it could be a useful tool for studying how mechanical forces influence airway function.
Applications in Toxicology and Drug Delivery
ALI models have broad applications in respiratory research. They are particularly useful for assessing the potential toxicity of inhaled substances. As noted in one study, these models can be used to assess inhalation toxicology endpoints. Research is exploring how ALI models can be used to improve drug delivery to the lungs. A recent study, for example, demonstrated that disrupting the airway mucus barrier with hydrogen enhanced the delivery of nebulized RNA, potentially reversing pulmonary fibrosis.
Establishing Reliable Exposure Systems
Creating a reliable ALI system for research requires careful control of several factors. Researchers have been working to optimize temperature, humidity, and the delivery of gases to the cells. A recent effort focused on adapting a horizontal-flow ALI-exposure system to ensure consistent and controlled exposure conditions. This is crucial for obtaining accurate and reproducible results.
The Future of Airway Research
The development of increasingly sophisticated ALI models represents a significant step forward in airway research. By providing a more realistic environment for studying lung cells, these models are helping scientists to better understand the mechanisms of respiratory diseases and to develop more effective treatments. The ability to manipulate factors like ECM composition and hydrogel stiffness opens up new avenues for investigating the complex interplay between cells, the environment, and disease processes. As research continues, ALI models are poised to play an increasingly important role in advancing our knowledge of lung health and disease.
These advancements offer promise for a deeper understanding of conditions ranging from asthma and chronic obstructive pulmonary disease (COPD) to infectious respiratory illnesses and the long-term effects of inhaled pollutants.
