Airway stem cell reconstitution by the transplantation of primary or pluripotent stem cell-derived basal cells
OA Version
Citation
Abstract
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 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), as well as ferret primary 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 and ferret donor cells transplanted into non-obese diabetic scid gamma (NSG) immunodeficient recipient mice similarly display multilineage airway epithelial differentiation in vivo. Our results may provide a step towards potential future syngeneic cell-based therapy for patients with diseases resulting from airway epithelial cell damage or dysfunction.
Description
2024
License
Attribution-ShareAlike 4.0 International