Airway stem cell reconstitution by the transplantation of primary or pluripotent stem cell-derived basal cells
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Cell Stem Cell. 2023 Aug 18;S1934-5909(23)00281-3. doi: 10.1016/j.stem.2023.07.014. Online ahead of print. PMID: 37625411.

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

Authors: Liang Ma 1Bibek R Thapa 2Jake A Le Suer 1Andrew Tilston-Lünel 3Michael J Herriges 1Andrew Berical 1Mary Lou Beermann 1Feiya Wang 4Pushpinder S Bawa 4Anat Kohn 1Alexandra B Ysasi 1Hirofumi Kiyokawa 1Taylor M Matte 1Scott H Randell 5Xaralabos Varelas 6Finn J Hawkins 1Darrell N Kotton 7

Affiliation:

  • 1Center for Regenerative Medicine, Boston University and Boston Medical Center, Boston, MA 02118, USA; The Pulmonary Center, Department of Medicine, Boston University School of Medicine, Boston, MA 02118, USA.
  • 2Center for Regenerative Medicine, Boston University and Boston Medical Center, Boston, MA 02118, USA; The Pulmonary Center, Department of Medicine, Boston University School of Medicine, Boston, MA 02118, USA; Department of Biology, Boston University, Boston, MA 02215, USA.
  • 3The Pulmonary Center, Department of Medicine, Boston University School of Medicine, Boston, MA 02118, USA; Department of Biochemistry, Boston University School of Medicine, Boston, MA 02118, USA.
  • 4Center for Regenerative Medicine, Boston University and Boston Medical Center, Boston, MA 02118, USA.
  • 5Marsico Lung Institute/Cystic Fibrosis Center, Department of Cell Biology and Physiology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
  • 6Department of Biochemistry, Boston University School of Medicine, Boston, MA 02118, USA.
  • 7Center for Regenerative Medicine, Boston University and Boston Medical Center, Boston, MA 02118, USA; The Pulmonary Center, Department of Medicine, Boston University School of Medicine, Boston, MA 02118, USA. Electronic address: dkotton@bu.edu.

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.

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

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