In vitro and ex vivo models of human asthma

In asthma, the airways undergo many structural and functional changes caused by environmental factors and genetic predisposition including a damaged epithelium, mucus hyper-secretion, thickening of the basement membrane, fibroblast and smooth muscle layer, angiogenesis and increased inflammation. To understand the underlying disease mechanisms, there is a need for a range of in vitro models that incorporate genetic and epigenetic features of the disease through use of asthma-derived cells. Asthma is an inflammatory disorder of the conducting airways which undergo distinct structural and functional changes leading to non-specific bronchial hyperresponsiveness (BHR) and airflow obstruction that fluctuate over time. It is a complex disease involving multiple genetic and environmental influences whose multifactorial interactions can result in a range of asthma phenotypes. Since our understanding of these gene–gene and gene–environment interactions is very poor, this poses a major challenge to the logical development of ‘models of asthma’. However, use of cells and tissues from asthmatic donors allows genetic and epigenetic influences to be evaluated and can go some way to reflect the complex interplay between genetic and environmental stimuli that occur in vivo . Current alternative approaches to in vivo animal models involve use of a plethora of systems ranging from very simple models using human cells (e.g. bronchial epithelial cells and fibroblasts) in mono- or co-culture, whole tissue explants (biopsies, muscle strips, bronchial rings) through to in vivo studies in human volunteers. Asthma research has been greatly facilitated by the introduction of fibreoptic bronchoscopy which is now a commonly used technique in the field of respiratory disease research, allowing collection of biopsy specimens, bronchial brushing samples, and bronchoalveolar lavage fluid enabling use of disease-derived cells and tissues in some of these models. Here, we will consider the merits and limitations of current models and discuss the potential of tissue engineering approaches through which we aim to advance our understanding of asthma and its treatment.