Transplantation of Induced Pluripotent Stem Cell-Derived Airway Epithelia with a Collagen Scaffold into the Nasal Cavity

The nasal cavity is covered with respiratory epithelia, including ciliated cells that eliminate foreign substances trapped in the mucus. In hereditary diseases such as primary ciliary dyskinesia and cystic fibrosis, respiratory epithelial functions are irreversibly impaired; however, no radical treatment has been established yet. Thus, we considered that the transplantation of normal airway epithelia (AE) into the nasal epithelia is one of the strategies that could lead to radical treatment in the future. In our previous study, human induced pluripotent stem cell-derived AE (hiPSC-AE) on the vitrigel membrane were transplanted into the scraped area of the nasal septal mucosa of nude rats. Although human-derived ciliated cells, club cells, and basal cells were observed, they were located in the cysts within the submucosal granulation tissue but not in the nasal mucosal epithelia and the transplanted cells may not contribute to the function of the nasal mucosa with this condition. Therefore, to achieve more functional transplantation, we prepared the graft differently in this study by wrapping the collagen sponge in hiPSC-AE on the vitrigel membrane. As a result, we found the transplanted cells surviving in the nasal mucosal epithelia. These results suggest that hiPSC-AE transplanted into the nasal cavity could be viable in the nasal mucosa. In addition, our method leads to the establishment of nasal mucosa-humanized rats that are used for the development of the drugs and therapeutic methods for hereditary diseases of nasal respiratory epithelia. Impact statementIn hereditary diseases such as primary ciliary dyskinesia, nasal mucosal epithelia are abnormally functioning; therefore, replacing aberrant cells with normal cells by cell transplantation is a promising candidate for radical treatment. In this study, we modified the graft preparation method and achieved the survival of transplanted human-derived airway epithelia in the nasal mucosal epithelia of nude rats. These successfully transplanted cells can contribute to the functional recovery of the nasal mucosa. Our transplantation method will contribute to developing therapeutic strategies for severe nasal mucosa dysfunction caused by hereditary diseases in the future.