Long-term Reconstruction of Human Airway Epithelium-like Structure in Vivo with hESCs-derived organoid cells

Human embryonic stem cells (hESCs) derived lung organoids (HLOs) provide a promising model to study human lung development and disease. However, whether HLO cells could reconstitute airway epithelial structure remains unclear. Here we established an orthotopic xenograft system for hESCs-derived HLOs, enabling stable reconstruction of human airway epithelium . Removal of the mouse airway epithelium by naphthalene (NA) treatment enabled xenografted organoid cells survival, differentiation, and reconstruction of airway pseudostratified epithelium in immune-compromised NSG mice. Compared to unsorted pool cells, CD47 cells generated more ciliated cells and possessed thicker pseudostratified epithelium. RNA-seq data revealed that CD47 cells highly expressed epithelial cell, lung progenitor, lung proximal cell and embryonic lung development associated genes. These data reveal that HLOs hold cell therapy potential in regenerative medicine by long-term reconstituting airway epithelium.