Utilizing a model of post-pneumonectomy (PNY) compensatory lung growth in mice, we previously observed an increase in numbers of a putative endogenous distal airway progenitor cell population (CCSPpos/pro-SPCpos cells located at bronchoalveolar duct junctions (BADJ)), at 3, 7, and 14 days after pneumonectomy, returning to baseline at 28 days post-PNY. As the origin of these cells is poorly understood, we evaluated whether bone marrow cells contributed to the pool of these or other cells during prolonged post-PNY lung regrowth. Naïve and sex-mismatched chimeric mice underwent left PNY and were evaluated at 1, 2 and 3 months for numbers of BADJ CCSPpos/pro-SPCpos cells and presence of donor-derived marrow cells engrafted as airway or alveolar epithelium. Non-chimeric mice were also examined at 12 months after PNY for numbers of BADJ CCSPpos/pro-SPCpos cells. Notably, the right accessory lobe (RAL) continued to grow disproportionately over 12 months, a novel finding not previously described. Assessment of lung mechanics demonstrated an increase in lung stiffness following PNY, which significantly diminished over one year, but remained elevated relative to 1 year-old naïve controls. However, the number of CCSPpos/pro-SPCpos BADJ cells ≥1 month following PNY was equivalent to that found in naïve controls even after 12 months of continued RAL growth. Notably, no donor bone marrow-derived cells engrafted as airway or alveolar epithelial cells, including those at the BADJ, up to 3 months after PNY. These studies suggest that lung epithelial cells, including CCSPpos/pro-SPCpos cells, are not replenished from marrow-derived cells during post-PNY lung growth in mice.
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