Development of a rat airway organoids model for studying chronic obstructive pulmonary disease

Abstract

Chronic obstructive pulmonary disease (COPD) poses global health challenges owing to limited treatment options and high rates of morbidity and mortality. Airway organoids have recently become a valuable resource for the investigation of respiratory diseases. However, limited access to clinical tissue samples hinders the use of airway organoids to study COPD. Therefore, alternative models that can mimic human airway pathology without relying on human tissues are needed. In this study, airway organoids were developed from tracheal epithelial cells obtained from 8-week-old Sprague-Dawley rats and exposed to lipopolysaccharide (LPS) to induce COPD-like characteristics. Exposure to LPS leads to structural changes in organoids, including an increase in goblet cells, a decrease in ciliated cells, increased mucin production, and elevated levels of pro-inflammatory cytokines. The COPD drugs erdosteine and R-HP210 effectively reduced mucin secretion, although none was able to restore the function of ciliated cells. Inflammatory markers responded differently, with ensifentrine and erdosteine significantly reducing cytokine levels. These results demonstrate that rat airway organoids replicate important aspects of human COPD pathology, thus providing an accessible, ethical, and clinically relevant alternative to human tissues and traditional animal models to enhance our understanding of COPD pathogenesis and evaluate potential treatments.

Keywords: Airway organoid model; Chronic obstructive pulmonary disease; Mucin; Sprague-Dawley rats.