Differentiation of human airway-organoids from induced pluripotent stem cells (iPSCs)

There was significant progress over the last decade in the ability to generate induced pluripotent stem cell (iPSC)-derived airway organoids. We and others have developed step-wise, directed differentiation protocols to recapitulate the key milestones in human airway development, generating iPSC-derived airway organoids that possess the major human airway cell types. These organoids have already shown feasibility for genetic disease modeling. They have great future potential for modeling a wider spectrum of lung diseases, interrogating disease mechanisms, predicting personalized drug responses, studying developmental lung biology, and ultimately may serve as candidates for future cell-based therapies for lung regeneration and repair. Herein we detail a step-by-step laboratory protocol to generate human airway organoids.