Pulmonary fibrosis: risk factors, pathogenesis and <i>in vivo/in vitro</i> experimental modeling

Abstract

Pulmonary fibrosis (PF) is a group of lung diseases characterized by scar formation and interstitial pneumonia with a mean life expectancy of 35 yearspost diagnosis. Risk factors for developing PF include external (environment) and internal (genetic risk factors). The central role in the formation of fibrosis is played by the massive myofibroblasts and the excessive deposition of extracellular matrix, including collagen I type. The main approaches for PF treatment is either lung transplantation or therapeutic treatment by antifibrotic drugs. However, for both approaches there are a number of limitations: for surgical the lack of donor organs and immune rejection of transplanted tissues, for therapeutic the drugs that are identified in animal studies fail in human clinical trials. Thus, there is a necessity for advancing of humanized in vitro models to improve treatments prior to human clinical trials. The development of different tissue (two-, three-dimensional) models has created systems capable of emulating human lung structure, function, and cell and matrix interactions, which have shown potential for in vitro drug testing. In this review, we focused on PF risk factors, development mechanisms, and a review of the main in vitro and in vivo models for studying PF.