Airway stem cell reconstitution by the transplantation of primary or pluripotent stem cell-derived basal cells
Liang Ma, Bibek R. Thapa, Jake A. Le Suer, Andrew Tilston-Lünel, Michael J. Herriges, Andrew Berical, Mary Lou Beermann, Feiya Wang, Pushpinder Bawa, Anat Kohn, Alexandra B. Ysasi, Hirofumi Kiyokawa, Taylor Matte, Scott H. Randell, Xaralabos Varelas, Finn Hawkins, Darrell N. Kotton
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 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.