Hypersecretion of mucus in asthma
Dr S Herrick, Dr R Gore & Dr D Thornton
Manchester University
2008 – 2011 Research Assistant
The development of a three-dimensional in vitro human airway model to understand the influence of epithelial-mesenchymal interactions on mucus production in hypersecretory respiratory disease.
Dr Sarah Herrick is a Research Fellow at Manchester University School of Medicine and Research Group Leader in Tissue Repair and Respiratory Biology.
Dr Robin Gore is a Consultant in Respiratory Medicine and Research Fellow at Manchester University.
Dr David Thornton is a Senior Lecturer in the Faculty of Life Sciences at Manchester University.
The immediate aim of this project is to develop a novel three-dimensional model of human asthmatic airways to enable the in vitro study of mucus production and replace animal studies. Asthma is a serious world-wide health problem with over 300 million people affected and prevalence increasing, especially among children. Abnormal mucus production is a major contributor to the pathology of asthma as well as other debilitating respiratory conditions such as cystic fibrosis and chronic pulmonary obstructive disease (COPD).
Chronic alterations to the mucus-producing capacity of the asthmatic airways occur as part of a spectrum of histopathological changes known as airway wall remodelling. Bronchial epithelial-mesenchymal interactions are thought to regulate several features of airway wall remodelling, but have not been investigated in relation to goblet cell hyperplasia and mucus hypersecretion. No animal ‘model’ of asthma exactly replicates the asthma phenotype of humans, and previous studies in mice may not be representative because of differences in the number and distribution of mucus-secreting cells between species, as well as other anatomical and immunological differences.
This project will establish a complex 3D co-culture human airway model using bronchial epithelial and bronchial fibroblast cells obtained from patients. The co-culture model will be used instead of animal studies to investigate key features of airway wall behaviour and identify disease-related changes, in particular goblet cell hyperplasia and mucus hypersecretion.
At present, no mucus-directed therapies are available for asthmatics and the factors that lead to excess mucus secretion during both chronic and acute severe asthma are not understood. Research using the human co-culture model could shed light on these factors and lead to new treatment options. The model will help to replace the use of animals for asthma research and could be adapted to study mucus hypersecretion in other serious respiratory conditions, such as COPD and cystic fibrosis.