Application of iPS cell-derived airway epithelial cells for cell-based therapy and disease models

Airway reconstruction is often required for patients with thyroid cancer, trauma, inflammation, or airway stenosis, with various treatments employing autografts and allografts. However, it is not easy to acquire an adequate quantity of cells and tissues for performing autografts and allografts. Thus, a new cell source for airway reconstruction is required. A large number of people also suffer from airway diseases such as cystic fibrosis and goblet cell hyperplasia caused by habitual cigarette smoking. Disease models using experimental animals to test available treatments or elucidate disease mechanisms have been reported. However, these disease models do not display the phenotypes observed in human airway disease or are not suitable as therapeutic models due to the different species. Furthermore, the use of primary human airway epithelial cells is expensive and cannot be stably obtained. Hence, a reliable human disease model must be constructed. In 2006 and 2007, it was discovered that induced pluripotent stem (iPS) cells established directly from somatic cells by overexpression of defined factors (Oct3/4, Sox2, Klf4, and c-Myc) had the capacity for self-renewal and pluripotency and could be differentiated into target cells, including airway epithelial cells. Thus, airway epithelial cells generated from iPS cells are expected to be potent candidates for the use of airway reconstruction and the construction of an airway disease model for elucidating the mechanisms and treatment of airway diseases. In this chapter, we review airway epithelial cell differentiation from iPS cells and their applications in airway reconstruction and disease models.