Airway stem cell reconstitution by the transplantation of primary or pluripotent stem cell-derived basal cells

Cell Stem Cell. 2023 Sep 7;30(9):1199-1216.e7. doi: 10.1016/j.stem.2023.07.014. Epub 2023 Aug 24.


Life-long reconstitution of a tissue's resident stem cell compartment with engrafted cells has the potential to durably replenish organ function. Here, we demonstrate the engraftment of the airway epithelial stem cell compartment via intra-airway transplantation of mouse or human primary and pluripotent stem cell (PSC)-derived airway basal cells (BCs). Murine primary or PSC-derived BCs transplanted into polidocanol-injured syngeneic recipients give rise for at least two years to progeny that stably display the morphologic, molecular, and functional phenotypes of airway epithelia. The engrafted basal-like cells retain extensive self-renewal potential, evident by the capacity to reconstitute the tracheal epithelium through seven generations of secondary transplantation. Using the same approach, human primary or PSC-derived BCs transplanted into NOD scid gamma (NSG) recipient mice similarly display multilineage airway epithelial differentiation in vivo. Our results may provide a step toward potential future syngeneic cell-based therapy for patients with diseases resulting from airway epithelial cell damage or dysfunction.

Keywords: airway basal cells; airway epithelial stem cell transplantation; directed differentiation; pluripotent stem cells; regeneration.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Cell- and Tissue-Based Therapy
  • Epithelial Cells
  • Epithelium
  • Humans
  • Mice
  • Mice, Inbred NOD
  • Mice, SCID
  • Pluripotent Stem Cells*