Blumer, SabrinaSabrinaBlumerKhan, PetraPetraKhanArtysh, NataliiaNataliiaArtyshPlappert, LindaLindaPlappertSavic, SpasenijaSpasenijaSavicKnudsen, LarsLarsKnudsenJonigk, DannyDannyJonigkKuehnel, Mark P.Mark P.KuehnelPrasse, AntjeAntjePrasseHostettler, Katrin E.Katrin E.Hostettler2024-01-102024-01-102023https://publica.fraunhofer.de/handle/publica/45861310.1101/2023.09.19.557680Honeycomb 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 establish in vitro- and in vivo models 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 model in vitro, and (3) investigated the cells’ behavior after instillation into bleomycin-challenged mice in vivo. Under the here tested in vitro- and in vivo conditions, 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.enpaper