“Engineered lung alveolar organoids to probe fibrotic remodeling in COVID-19 induced lung injuries”
Claudia Loebel, MD/PhD and Matthew Davidson, PhD (PI: Jason Burdick)
Abstract: Using engineered alveolar organoids and secreted extracellular matrix (ECM) labeling and stiffening techniques, we will monitor cell behavior in response to mechanical perturbations and antiviral treatment. Specifically, we will test the hypothesis that local ECM stiffening promotes alveolar epithelial cell dysfunction (e.g., impaired proliferation, dedifferentiation) and accumulation of fibroblasts. In addition, we will examine the effect of currently tested COVID-19 drugs on alveolar epithelial cell function and fibrotic signaling.
Relevance: The Center for Engineering MechanoBiology strives to advance the relationship between cellular/tissue mechanics and biology for a wide variety of applications. The COVID-19 pandemic is still emerging and will have a tremendous impact on health and society worldwide. As a disease that is largely affecting the respiratory system, cellular response via mechanical cues are likely to play a key role in tissue repair and regeneration. The proposed work will establish a new disease modeling approach for studying ARDS-induced fibrotic remodeling that will also be extensible to other fibrotic diseases within the lung. Additionally, examining the potential pro- or anti-fibrotic effects of current COVID-19 therapies will inform current clinical decisions and their long-term effects on patient outcomes.