a Department of Cellular and Integrative Physiology, School of Medicine , Fukushima Medical University , Fukushima , Japan.
b Department of Otolaryngology Head and Neck Surgery, Graduate School of Medicine , Kyoto University , Kyoto , Japan.
Channels (Austin). 2019 Dec;13(1):227-234. doi: 10.1080/19336950.2019.1628550.
induced pluripotent stem (iPS) cells can be differentiated into various cell types, including airway epithelial cells, since they have the capacity for self-renewal and pluripotency. Thus, airway epithelial cells generated from iPS cells are expected to be potent candidates for use in airway regeneration and the treatment of airway diseases such as cystic fibrosis (CF). Recently, it was reported that iPS cells can be differentiated into airway epithelial cells according to the airway developmental process. These studies demonstrate that airway epithelial cells generated from iPS cells are equivalent to their in vivo counterparts. However, it has not been evaluated in detail whether these cells exhibit physiological functions and are fully mature. Airway epithelial cells adequately control water volume on the airway surface via the function of Cl channels. Reasonable environments on the airway surface cause ciliary movement with a constant rhythm and maintain airway clearance. Therefore, the generation of functional airway epithelial cells/tissues with Cl channel function from iPS cells will be indispensable for cell/tissue replacement therapy, the development of a reliable airway disease model, and the treatment of airway disease. This review highlights the generation of functional airway epithelial cells from iPS cells and discusses the remaining challenges to the generation of functional airway epithelial cells for airway regeneration and the treatment of airway disease.
诱导多能干细胞(iPS 细胞)具有自我更新和多能性,因此可以分化为多种细胞类型,包括气道上皮细胞。因此,源自 iPS 细胞的气道上皮细胞有望成为气道再生和治疗囊性纤维化(CF)等气道疾病的有力候选物。最近,有报道称 iPS 细胞可以根据气道发育过程分化为气道上皮细胞。这些研究表明,源自 iPS 细胞的气道上皮细胞与体内的气道上皮细胞相当。然而,这些细胞是否具有生理功能并完全成熟,尚未进行详细评估。气道上皮细胞通过 Cl 通道的功能在气道表面上充分控制水分量。合理的气道表面环境会引起具有恒定节律的纤毛运动,并保持气道清除。因此,从 iPS 细胞生成具有 Cl 通道功能的功能性气道上皮细胞/组织对于细胞/组织替代疗法、可靠的气道疾病模型的开发以及气道疾病的治疗将是不可或缺的。本综述强调了从 iPS 细胞生成功能性气道上皮细胞,并讨论了为气道再生和气道疾病治疗生成功能性气道上皮细胞所面临的剩余挑战。