Engineered cell and tissue models of pulmonary fibrosis

Abstract

Pulmonary fibrosis includes several lung disorders characterized by scar formation and Idiopathic Pulmonary Fibrosis (IPF) is a particularly severe form of pulmonary fibrosis of unknown etiology with a mean life expectancy of 3years' post-diagnosis. Treatments for IPF are limited to two FDA approved drugs, pirfenidone and nintedanib. Most lead candidate drugs that are identified in pre-clinical animal studies fail in human clinical trials. Thus, there is a need for advanced humanized in vitro models of the lung to improve candidate treatments prior to moving to human clinical trials. The development of 3D tissue models has created systems capable of emulating human lung structure, function, and cell and matrix interactions. The specific models accomplish these features and preliminary studies conducted using some of these systems have shown potential for in vitro anti-fibrotic drug testing. Further characterization and improvements will enable these tissue models to extend their utility for in vitro drug testing, to help identify signaling pathways and mechanisms for new drug targets, and potentially reduce animal models as standard pre-clinical models of study. In the current review, we contrast different in vitro models based on increasing dimensionality (2D, 2.5D and 3D), with added focus on contemporary 3D pulmonary models of fibrosis.

Keywords: Anti-fibrotic drug; Decellularized lung matrices; Hydrogel; Idiopathic Pulmonary Fibrosis; Lung organoid; Lung spheroid; Lung-on-chip; Precision cut lung tissue (PCLT); Pulmonary fibrosis; Three-dimensional (3D) culture; Two-dimensional (2D) culture; Two-point-five-dimensional (2.5D) culture; in vitro models.