Neonatal lung-derived SSEA-1⁺ cells exhibited distinct stem/progenitor characteristics and organoid developmental...

Stem/progenitor cells, because of their self-renewal and multiple cell type differentiation abilities, have good potential in regenerative medicine. We previously reported a lung epithelial cell population that expressed the stem cell marker SSEA-1 was abundant in neonatal but scarce in adult mice. In the current study, neonatal and adult mouse-derived pulmonary SSEA-1⁺ cells were isolated for further characterization. The results showed that neonatal-derived pulmonary SSEA-1⁺ cells highly expressed lung development-associated genes and had enhanced organoid generation ability compared with the adult cells. Neonatal pulmonary SSEA-1⁺ cells generated airway-like and alveolar-like organoids, suggesting multilineage cell differentiation ability. Organoid generation of neonatal but not adult pulmonary SSEA-1⁺ cells was enhanced by fibroblast growth factor 7 (FGF 7). Furthermore, neonatal pulmonary SSEA-1⁺ cells colonized and developed in decellularized and injured lungs. These results suggest the potential of lung-derived neonatal-stage SSEA-1⁺ cells with enhanced stem/progenitor activity and shed light on future lung engineering applications.