Bone marrow-derived angiogenic cells restore lung alveolar and vascular structure after neonatal hyperoxia in infant mice.
Neonatal hyperoxia impairs vascular and alveolar growth in mice and decreases endothelial progenitor cells. To determine the role of bone marrow-derived cells in restoration of neonatal lung structure after injury, we studied a novel bone marrow myeloid progenitor cell population from Tie2-green fluorescent protein (GFP) transgenic mice (bone marrow-derived angiogenic cells; BMDAC). We hypothesized that treatment with BMDAC would restore normal lung structure in infant mice during recovery from neonatal hyperoxia. Neonatal mice (1-day-old) were exposed to 80% oxygen for 10 days. BMDACs (1 x 10(5)), embryonic endothelial progenitor cells, mouse embryonic fibroblasts (control), or saline were then injected into the pulmonary circulation. At 21 days of age, saline-treated mice had enlarged alveoli, reduced septation, and a reduction in vascular density. In contrast, mice treated with BMDAC had complete restoration of lung structure that was indistinguishable from room air controls. BMDAC comprised 12% of distal lung cells localized to pulmonary vessels or alveolar type II (AT2) cells and persist (8.8%) for 8 wk postinjection. Coculture of AT2 cells or lung endothelial cells (luEC) with BMDAC augmented AT2 and luEC cell growth in vitro. We conclude that treatment with BMDAC after neonatal hyperoxia restores lung structure in this model of bronchopulmonary dysplasia.
Balasubramaniam
Vivek
V
Pediatric Heart Lung Center, Department of Pediatrics, University of Colorado-Denver, 12800 E. 19th Ave., Aurora, CO 80045, USA. vivek.balasubramaniam@ucdenver.edu
Ryan
Sharon L
SL
Seedorf
Gregory J
GJ
Roth
Emily V
EV
Heumann
Thatcher R
TR
Yoder
Mervin C
MC
Ingram
David A
DA
Hogan
Christopher J
CJ
Markham
Neil E
NE
Abman
Steven H
SH
D000818:Animals; D000831:Animals, Newborn; D001854:Bone Marrow Cells / Q000166:cytology*; D049109:Cell Proliferation; D003114:Colony-Forming Units Assay; D042783:Endothelial Cells / Q000166:cytology* / Q000637:transplantation; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D018496:Hyperoxia / Q000473:pathology*; D051379:Mice; D018919:Neovascularization, Physiologic; D010641:Phenotype; D011650:Pulmonary Alveoli / Q000098:blood supply* / Q000473:pathology*; D013997:Time Factors