J Respir Med Lung Dis | Volume 4, Issue 1 | Research Article | Open Access
Igal Germanguz#, Evelyn Aranda#, Jennifer C Xiong, Natalia Kissel, Alexandra Nichols, Eddie Gadee and John D O’Neill*
Xylyx Bio, 760 Parkside Avenue, Brooklyn, New York, USA
#Both authors equally contributed to this work
*Correspondance to: John D O’Neill
Fulltext PDFIdiopathic Pulmonary Fibrosis (IPF) is an irreversible and uniformly fatal lung disease marked by destruction and scarring of the lung parenchyma and progressive loss of respiratory function. IPF affects nearly 3 million people worldwide, and annual mortality in the US alone exceeds 40,000. Nintedanib and pirfenidone, the only drugs approved for the treatment of IPF, slow progression but do not cure the disease. Consequently, there is a pressing need for effective treatments beside lung transplantation. Unfortunately, predictive models of IPF are not available, underscoring the critical need for physiologically relevant in-vitro substrates that enable quantitative and mechanistic studies of human IPF. Here we report the development and characterization of a human pulmonary fibrosisspecific cell culture substrate comprised of intact fibrotic lung extracellular matrix that recapitulates the human IPF disease environment in vitro. We document the activation and disease-specific phenotype of human lung fibroblasts cultured in the IPF disease-specific substrate and establish feasibility of testing antifibrotic agents using this substrate. Altogether, our results demonstrate the applicability of this fibrosis-specific substrate for 3D in-vitro models of IPF and cell-based assays in early-stage drug discovery.
3D cell culture; Drug testing; Extracellular matrix; Idiopathic pulmonary fibrosis; In-vitro models; Lung disease; Lung fibroblasts; Scaffolds
Germanguz I, Aranda E, Xiong JC, Kissel N, Nichols A, Gadee E, et al. Fibrotic Human Lung Extracellular Matrix as a Disease-Specific Substrate for Models of Pulmonary Fibrosis. J Respir Med Lung Dis. 2019; 4(1): 1043.