Effect of the Physical Environment on Airway Cell Differentiation and Behaviour
Herein, we have projects which focus on evaluating the effect of the physical environment on behaviour and function of airway epithelium. Over the last few years, we have developed ex vivo models which allow us to effectively evaluate the effect of physical factors at an organ level as well as a cellular level. These models include whole lung scaffolds maintained in biomimetic bioreactor systems as well as an alveolus-on-chip system with dynamic cyclical stretch.
Project 1: Effect of biophysical cues on differentiation of induced pluripotent stem cell-derived airway epithelial cells
(Soleas et al., 2020)
While the effect of chemical stimuli (i.e. growth factors) on pluripotent stem cells are well understood and used to guide directed differentiation towards lung epithelium, little is known about how biophysical cues impact differentiation and maturity of pluripotent stem cells. Given that the lung develops in response to chemical signals within a highly dynamic mechanical environment of cyclic strain, pressure and a complex branching tubular architecture, one can imagine a significant effect of mechanical cues on airway progenitor cell fate. We and others have shown that the mechanical environment can be manipulated to produce predictable fate choices in stem and progenitor cells. Continuing with these studies, we are currently exploring the effect of biomimetic geometry and substrate stiffness on differentiation of distal alveolar epithelial cells and hypothesize that these physical factors will impact epithelial cell maturity and function.
Project 2: The effect of mechanical stress on decellularized lung scaffolds and airway epithelial cells
It is well understood that physical factors such as changes in pressure and stiffness can induce phenotypic and functional changes in lung, both at a structural level and at the cellular level. In certain cases, exposure to certain physical factors can lead to the development of pathological conditions in the lung. This is the case for Pulmonary Fibrosis (PF) and Ventilator-Induced Lung Injury (VILI). We are currently investigating the impact of aberrant cyclical stretch on lung scaffolds and alveolar epithelial cells in order to gain a better understanding of the underlying mechanisms of disease resulting in PF and VILI. This knowledge will allow us to develop effective treatment solutions.
