Human iPSC-derived Alveolar Epithelial Cells

Human iPSC-derived Alveolar Epithelial Cells (iPSC-AECs) are cultured lung epithelial cells derived from human induced pluripotent stem cells (iPSCs) in a stepwise fashion to mimic embryonic lung development from definitive endoderm to NKX2.1+ respiratory progenitors and ultimately to type I (AEC I) and type II (AEC II) alveolar epithelial cells. Lineage-specific cultures of AEC I and AEC II have distinct morphological and phenotypic properties recapitulating the alveolar epithelium in vivo. For example, AEC II are cuboidal and rich in lamellar bodies, and robustly express SFTPC and ABCA3, while AEC I are extremely flattened and elongated with a characteristic "spiky" morphology and express AQP5 and PDPN. These cells also maintain a number of key physiological properties of the native alveolar epithelium, including surfactant production and secretion, development of tight junction protein complexes and a barrier, and innate cytokine response to inflammatory or infectious insults. AEC II also maintain the capacity to differentiate into AEC I in culture, allowing for in vitro recapitulation of aspects of alveolar repair and regeneration.

Owing to their immunoreactive state and sensitivity to respiratory pathogens, these cells have been used to study viral tropism, host-pathogen interactions, and innate immune response. These cells have been applied to many respiratory disease areas and modeling applications, including pulmonary fibrosis, acute lung injury, surfactant dysfunction, and chronic lung disease. As such, these cells are being leveraged for drug screening, toxicity testing, nanoparticle exposure, as well as advanced applications like air-liquid interface, 3D alveolospheres, and lung-on-chip models.