[NYAS Fibrosis 2020] Identification of Novel Antifibrotic Treatments Using Co-Cultures of Human Primary Epithelial Cells and Fibroblasts

File Name/Number:
NYAS Fibrosis 2020


Research and treatment of idiopathic pulmonary fibrosis (IPF) has traditionally focused on fibroblasts and mechanisms driving myofibroblast activation, an approach that neglects the diverse, multicellular nature of the lung and its contribution to disease. Development of more complex, physiologically relevant models of fibrosis are needed to further our understanding of IPF. As part of the BioMAP® phenotypic platform, assays modeling fibrosis include complex fibroblast-epithelial co-cultures that model paracrine interactions between these two proximally located cell types. Co-culture models include either small airway epithelial cells modeling lung fibrosis, or proximal renal tubule epithelial cells modeling fibrotic disease of the kidney. Assays were used to screen well-characterized compounds representing different mechanisms of action to evaluate impact on antifibrotic and anti-inflammatory potential. Several compounds demonstrated greater antifibrotic potential in co-culture versus monoculture systems, suggesting an impact on paracrine signaling. For example, the chemokine inhibitor bindarit decreased fibrillar collagen expression in both co-culture systems but not in the fibroblast monoculture. Additionally, the CFTR potentiator drug ivacaftor mediated small decreases in collagen levels in monocultures that was further decreased in co-culture systems. Targets of these compounds may represent novel mechanisms involved in the pathogenesis of fibrotic disease.