Fundamentals for modelling the airway wall

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Our body, organs, and tissues are made up of cells that are held together by a kind of glue called the extracellular matrix (ECM). In this three-dimensional environment, cells stick to each other and to the extracellular matrix. Mechanical properties of the extracellular matrix, such as stiffness, determine the fate and function of the attached cells. Therefore, it is no surprise that changes in the composition and stiffness of the extracellular matrix can have a detrimental effect on the function of the organ made up of these cells.

This doctoral research by Roderick de Hilster demonstrated that during chronic obstructive pulmonary disease (COPD), a deadly disease without a cure, the communication between cells and the extracellular matrix is disrupted.

Three-dimensional culture models have been developed to understand how fibroblasts are affected. Fibroblasts are cells from the connective tissue of the lung and airways. These culture models help to investigate how fibroblasts respond to the extracellular matrix from healthy and diseased lungs. Additionally, the influence of different stiffness levels on these cells is also examined. It appears that higher-than-normal stiffness of the extracellular matrix promotes airway diseases. The results pave the way for the development of new therapies to treat COPD by targeting the disrupted extracellular matrix.