Engineering 3D Lung Models with Magnetically Labeled Fibroblasts

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Presenter(s)

Dema Essmaeil

Abstract or Description

Idiopathic pulmonary fibrosis (IPF) is a chronic disease that progressively affects the lung, leading to respiratory failure. The extracellular matrix (ECM), the proteins and other molecules supporting the cells in our tissues, plays an important role in lung development, repair, and disease. Biophysical and biochemical signals produced by the ECM regulate the function of various cells including fibroblasts in the lungs. Fibroblasts are important lung structural cells providing production and repair of the ECM. There is an increased ECM deposition during IPF that results in increased tissue stiffness and a positive feedback loop of fibroblast activation. The Magin lab has advanced technologies for engineering models of lung tissue and created hybrid-hydrogels to mimic, decouple, and study biochemical and biophysical changes in the cellular microenvironments. In my project, I decellularized human lung from healthy and fibrotic donors and incorporated the resulting proteins and other molecules into 3D hybrid hydrogel models. In these models, we recreated lung geometry by magentically aggregating a layer of fibroblasts around stem cell-derived epithelial cell spheroids. We confirmed the decellularizaion process by analyzing the residual DNA that was below 50 ng/mg in both healthy and fibrotic samples. We selected fibroblast densities and aggregation time to create the structure that best replicates distal lung architecture. By embedding these structures in hybrid-hydrogels containing either healthy or fibrotic dECM, we will investigate the role of both cellular and extracellular components in the progression of IPF. This model will allow for patient-centered research by using human cells and dECM to study fibrotic phenotypes in a system that mimics the geometry, composition, and biomechanical properties of lung tissue.

Mentor

Chelsea Magin