The use of cultured human alveolar basal cells to mimic honeycomb formation in idiopathic pulmonary fibrosis

Abstract

SummaryHoneycomb cysts (HC) within the alveolar region are distinct histopathological features in the lungs of idiopathic pulmonary fibrosis (IPF) patients. HC are lined with basal cells (BC), or with a bronchiolar-like epithelium composed of basal-, ciliated- and secretory epithelial cells. By using cultured IPF patient-derived alveolar BC, we aimed to establishin vitro- andin vivomodels to mimic HC formation in IPF. In order to do so, we cultured the cells (1) on an air liquid interface (ALI) or (2) in a three dimensional (3D) organoid modelin vitro, and (3) investigated the cells’ behavior after instillation into bleomycin-challenged micein vivo. Under the here testedin vitro- andin vivoconditions, alveolar BC differentiate and formed HC-like structures, which closely resemble HC within the IPF lung. These models therefore represent powerful tools to study HC formation, and its potential therapeutic inhibition in IPF.