Generation of alveolar organoids from human induced pluripotent stem cells using a stirred-tank bioreactor

ABSTRACT: Organoids are increasingly establishing themselves as a valuable, patient-centered alternative to preclinical animal models as they are highly complex models for organ development studies and, in particular, robust disease models for mechanistic investigations and therapy response assessments. We previously established a very simple and practical protocol for producing iPSC-LuOrgs from pre-differentiated embryoid bodies without the need of a gel-like extracellular matrix using a stirred bioreactor system. Here, we investigated now an adapted protocol for the generation of iPSC-LuOrgs directly from iPSCs in stirred suspension and performed a comprehensive cellular and molecular characterization, including single-cell RNA sequencing, of the resulting LuOrgs differentiated in a bioreactor. Generated lung structures appeared to be less differentiated and were predominately of alveolar nature. Fibroblasts and bronchial epithelial cells were inefficiently generated. Therefore, pre-differentiation of iPSCs, e.g., in embryoid bodies seems to be a necessary prerequisite for the efficient generation of iPSC-LuOrgs, which then exhibit alveolar and bronchial cell types and structures supported by mesenchymal cells.

ORGANISM(S): Homo sapiens

PROVIDER: GSE337365 | GEO | 2026/08/26

REPOSITORIES: GEO