Use of Lung Organoids to Model Development andDisease Ex Vivo

During the las t years, organoid models have become a powerfultool to s tudy lung development and disease. Our research focuson the use of three-dimensional lung organoid sys tems fromadult somatic s tem cells and induced pluripotent s tem cells (iPSCs)for modeling of lung development and disease aiming atthe es tablishment of novel therapeutic s trategies. For ins tance,we es tablished a ۳D murine bronchioalveolar lung organoid(BALO) model that allows clonal expansion and self-organizationof FACS-sorted bronchioalveolar s tem cells (BASCs)upon co-culture with lung-resident mesenchymal cells. BALOsyield a highly branched ۳D s tructure within ۲۱ days of culture, mimicking the cellular composition of the bronchioalveolarcompartment as defined by single-cell RNA sequencingand fluorescence as well as electron microscopic phenotyping.Additionally, BALOs support engraftment and maintenanceof different cell types thereby open numerous new avenues tos tudy lung development, infection, and regenerative processesin vitro.