title: Endogenous distal airway progenitor cells, lung mechanics, and disproportionate lobar growth following long-term postpneumonectomy in mice.
abstract: Using a model of postpneumonectomy (PNY) compensatory lung growth in mice, we previously observed an increase in numbers of a putative endogenous distal airway progenitor cell population (CCSP(pos) /pro-SPC(pos) cells located at bronchoalveolar duct junctions [BADJs]), 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 CCSP(pos) /pro-SPC(pos) cells and presence of donor-derived marrow cells engrafted as airway or alveolar epithelium. Nonchimeric mice were also examined at 12 months after PNY for numbers of BADJ CCSP(pos) /pro-SPC(pos) 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 1 year, but remained elevated relative to 1-year-old naïve controls. However, the number of CCSP(pos) /pro-SPC(pos) 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 CCSP(pos) /pro-SPC(pos) cells, are not replenished from marrow-derived cells during post-PNY lung growth in mice.
authors.affiliation: Department of Medicine, University of Vermont College of Medicine, Burlington, VT, USA.
authors.forename: Philip
authors.initials: P
authors.lastname: Eisenhauer
authors.forename: Benjamin
authors.initials: B
authors.lastname: Earle
authors.forename: Roberto
authors.initials: R
authors.lastname: Loi
authors.forename: Viranuj
authors.initials: V
authors.lastname: Sueblinvong
authors.forename: Meagan
authors.initials: M
authors.lastname: Goodwin
authors.forename: Gilman B
authors.initials: GB
authors.lastname: Allen
authors.forename: Lennart
authors.initials: L
authors.lastname: Lundblad
authors.forename: Melissa R
authors.initials: MR
authors.lastname: Mazan
authors.forename: Andrew M
authors.initials: AM
authors.lastname: Hoffman
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Weiss
mesh_terms: D000818:Animals; D008168:Lung / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D011013:Pneumonectomy / Q000379:methods*; D015656:Respiratory Mechanics / Q000235:genetics / Q000502:physiology*; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism / Q000502:physiology*
keywords: Bronchioalveolar stem cell; Lung regeneration; Postpneumonectomy lung growth; Progenitor cell