World COPD Day 2025

Advancing COPD research with a physiologically relevant ALI model

It’s World COPD Day 2025, a day created to raise awareness of Chronic Obstructive Pulmonary Disease (COPD) and its symptoms. At Cellomatics we have developed a specialised model to capture the complex, chronic, features of COPD. Take a look at our blog below to learn more. 

Chronic Obstructive Pulmonary Disease (COPD) remains a major global health challenge. Despite decades of public health campaigns, advances in treatment, and increased regulatory controls on smoking, COPD is among the leading causes of death and disability worldwide. According to the World Health Organisation, nearly 90% of COPD-related deaths in people under 70 years old occur in low‑ and middle‑income countries [1]. Tobacco smoking accounts for over 70% of COPD cases in high‑income countries, making it the dominant risk factor in many regions [2]. At the same time, occupational exposures, air pollution, and other environmental hazards contribute significantly in settings where regulation is weaker [5].

Clinically, COPD is characterised by progressive airflow limitation, chronic inflammation, and structural remodelling of the airway epithelium. One of its hallmarks is mucus hypersecretion combined with impaired mucociliary clearance, which compromises the airway’s ability to remove harmful particles or pathogens [3,4]. Over time, this contributes to repeated exacerbations, a persistent cough, breathlessness, and a deteriorating quality of life.

Traditional in-vitro models—such as submerged cultures of airway epithelial cells—are often insufficient for capturing the complex, chronic features of COPD. Submerged models typically lack the differentiated cellular architecture, long-term stability, and functional barrier properties that characterise the human airway in vivo. They do not support the physiological mucus production or ciliary activity observed in differentiated airway tissue, limiting their utility for modelling chronic disease processes or environmental exposures.

To overcome these limitations, Cellomatics has developed a specialised Air‑Liquid Interface (ALI) model using human bronchial epithelial cells (HBEpC) that encourages differentiation into a pseudostratified epithelium, containing basal cells, ciliated cells, and mucus-secreting goblet cells. The result is a tissue-like structure closely mimicking the human bronchial epithelium, which supports long-term culture, repeated exposures, and functionally relevant behaviour.

One of the key advantages of the HBEpC‑ALI system is its ability to support chronic exposure protocols. Unlike conventional cultures, it remains viable over extended periods, allowing researchers to model repeated or sustained exposure to irritants like cigarette smoke extract (CSE), acrolein, or inflammatory cytokines—conditions that more closely reflect the real-world environment of a COPD patient. Importantly, the ALI model preserves epithelial barrier integrity, cilia function, and mucus secretion, enabling a comprehensive, physiologically relevant readout.

Using this model, Cellomatics has demonstrated disease-relevant responses consistent with COPD pathology. When HBEpC-ALI cultures are treated with Th2 cytokines such as IL‑13 and IL‑4, there is a robust upregulation of MUC5AC and MUC5B, two mucin genes central to mucus production [Figure 1A and 1B]. More strikingly, chronic exposure to 5% cigarette smoke extract (CSE) or acrolein induces a dramatic increase in mucin gene expression: MUC5AC levels rise by roughly 300‑fold, while MUC5B increases around 75‑fold, mirroring pathological mucus overproduction seen in COPD [Figure 1C and 1D].

To confirm that these transcriptional changes translate into protein-level differences, immunohistochemistry staining has demonstrated elevated MUC5AC and MUC5B in cytokine-exposed ALI cultures—providing direct visual evidence of disease-relevant mucus production [See Figure 2].