PhD defence M.C. (Cinta) Iriondo Martinez

Below is a brief summary of the dissertation:  

The human lung is essential for gas exchange, and its critical role in sustaining life is evident when its function is impaired by diseases, such as congenital abnormalities or infections. Respiratory diseases are among the leading causes of morbidity and mortality, with young children being particularity vulnerable to disease-causing agents. To better understand the origin and progression of pulmonary diseases, several models have been developed. Traditionally, immortalized epithelial cell lines and animal models have been employed in fundamental and pre-clinical research to investigate different aspects of lung diseases. Although each of these models has provided valuable insights, they often have limitations in extrapolating findings to human patients and consequently lack sufficient predictive power. Therefore, there is an urgent need to improve in vitro pulmonary models to more accurately reflect the complexity of the human lungs’ physiology. Recently, several advanced in vitro models have been developed, each contributing to the field, but they come at a price since many of these models are technically challenging, exhibit low throughput, and frequently rely on tumor-derived cell lines. In addition, some fail to distinguish between the gas-exchanging alveolar and conducting airway models, which have distinct functions, cellular composition, and disease susceptibilities. This thesis explored the development of advanced in vitro models for both the airway and alveoli, incorporating primary cells derived from human lung resection material. The advanced culture systems consisted of three-dimensional scaffolds, or a dynamic flow system to improve some of the limitations of current models.