Potential of Alveolar Tissue Models as Disease Models in Pharmaceutical Sciences

Engineered alveolar tissue models that recapitulate physiological and pharmacological characteristics of native distal lung tissue would be invaluable research tools, with broad applications as pharmacological models of normal and pathological tissues, and novel venues for investigation of pulmonary toxicology and infectivity. The refinement of traditional 2D models used to investigate drug permeability in lung tissue [142, 154] will result in a more physiologically relevant model to study drug permeation [132, 155]. Tissue engineering approaches can be used to generate complex 3D alveolar tissue models containing the epithelial, microvascular, and connective tissue components. Specifically, these approaches will yield high-fidelity models of pediatric pulmonary diseases such as bronchopulmonary dysplasia and cystic fibrosis, and adult pulmonary diseases such as emphysema and particulate lung disease. Some neonatal pulmonary diseases, occurring secondary to pulmonary hypoplasia, are hallmarked by the aberrant development of epithelial and vascular components ofthe lung [156]. Therefore, a more realistic 3D alveolar tissue model would be useful for investigating pathological developmental processes that are at the root of pediatric chronic lung disease.

In addition to developing disease models of (pediatric) pulmonary diseases, existing in-vitro 2D cell culture models of pulmonary toxicology [157] could be extended to 3D tissue models. In a recent investigation of a patient who succumbed to the fatal H5N1 avian influenza virus, the alveolar epithelial cells were found to be a major site of H5N1 replication [158]. Recent reports focus on the use of 2D respiratory epithelial cell culture models for studying pathogenesis of influenza viruses, as well as environmental toxicants [159]. We contend that extending these 2D systems to 3D alveolar tissue constructs will provide a more realistic and physiologically correct pharmacological model for developing of antiviral drugs or vaccines targeting alveolar epithelial cells.

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