Airway regeneration using iPS cell-derived airway epithelial cells with Cl- channel function

Channels (Austin). 2019 Dec;13(1):227-234. doi: 10.1080/19336950.2019.1628550.

Abstract

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.

Keywords: CFTR; Cl channel; airway epithelial cells; cystic fibrosis; iPS cells.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Cell Differentiation
  • Chloride Channels / genetics
  • Chloride Channels / metabolism*
  • Chlorides / metabolism
  • Epithelial Cells / cytology*
  • Epithelial Cells / metabolism
  • Humans
  • Induced Pluripotent Stem Cells / cytology*
  • Induced Pluripotent Stem Cells / metabolism
  • Lung / cytology
  • Lung / physiopathology*
  • Regeneration

Substances

  • Chloride Channels
  • Chlorides

Grants and funding

This study was supported by the Japan Society for the Promotion of Science [17K16932] and the Takeda Science Foundation [SO29028].