Missing Nuts and Bolts: Translating Pulmonary Fibrosis from Preclinical Murine Models to Human Clinical Trials

Excerpt

The importance of promoting candidate idiopathic pulmonary fibrosis (IPF) drugs from preclinical trials in murine models to clinical trials in humans is highlighted in a recent editorial in The Lancet Respiratory Medicine [1]. The editorial appropriately focuses on the important impact of IPF clinical trials and drug testing on the three essential components of human health: how the patient feels, functions, and survives [1]. However, as the editorial recognizes, preclinical testing often relies on murine models of pulmonary fibrosis that are induced chemically using bleomycin, which causes histopathological and biochemical changes that make them quite different from human patients. Given that no murine or preclinical models of pulmonary fibrosis are able to recapitulate every aspect of human chronic lung fibrosis, we feel that novel approaches to modeling IPF should be employed. These include 2D (primary lung cells: fibroblasts, alveolar epithelial cells, macrophages, endothelial cells, etc.), co-culture models, 3D hydrogels, precision-cut lung slices, lung organoids that use primary lung cells/tissues derived from either IPF patients or mouse models of pulmonary fibrosis, and Lung-on-Chip. These techniques should be used in combination with preclinical murine models to create complementary models of pulmonary fibrosis as part of the key drug testing regulatory workflow. The use of novel imaging and functional assays in preclinical murine models [2, 3] during preclinical drug testing will more effectively translate to human physiological outcomes. …