Bone marrow-derived angiogenic cells restore lung alveolar and vascular structure after neonatal hyperoxia in infant mice

Vivek Balasubramaniam, Sharon L. Ryan, Gregory J. Seedorf, Emily V. Roth, Thatcher R. Heumann, Mervin Yoder, David Ingram, Christopher J. Hogan, Neil E. Markham, Steven H. Abman

Research output: Contribution to journalArticle

77 Citations (Scopus)

Abstract

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 × 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.

Original languageEnglish
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Volume298
Issue number3
DOIs
StatePublished - Mar 2010

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Hyperoxia
Blood Vessels
Bone Marrow
Lung
Bone Marrow Cells
Endothelial Cells
Myeloid Progenitor Cells
Bronchopulmonary Dysplasia
Pulmonary Circulation
Growth
Coculture Techniques
Green Fluorescent Proteins
Transgenic Mice
Fibroblasts
Air
Oxygen
Wounds and Injuries
Therapeutics

Keywords

  • Alveolar type 2 cell
  • Bronchopulmonary dysplasia
  • Endothelial cell
  • Oxygen
  • Stem cell

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Physiology (medical)
  • Cell Biology
  • Physiology

Cite this

Bone marrow-derived angiogenic cells restore lung alveolar and vascular structure after neonatal hyperoxia in infant mice. / Balasubramaniam, Vivek; Ryan, Sharon L.; Seedorf, Gregory J.; Roth, Emily V.; Heumann, Thatcher R.; Yoder, Mervin; Ingram, David; Hogan, Christopher J.; Markham, Neil E.; Abman, Steven H.

In: American Journal of Physiology - Lung Cellular and Molecular Physiology, Vol. 298, No. 3, 03.2010.

Research output: Contribution to journalArticle

Balasubramaniam, Vivek ; Ryan, Sharon L. ; Seedorf, Gregory J. ; Roth, Emily V. ; Heumann, Thatcher R. ; Yoder, Mervin ; Ingram, David ; Hogan, Christopher J. ; Markham, Neil E. ; Abman, Steven H. / Bone marrow-derived angiogenic cells restore lung alveolar and vascular structure after neonatal hyperoxia in infant mice. In: American Journal of Physiology - Lung Cellular and Molecular Physiology. 2010 ; Vol. 298, No. 3.
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abstract = "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 × 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.",
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