Mesenchymal stem cells protect against neonatal rat hyperoxic lung injury

Expert Opin Biol Ther. 2013 Jun;13(6):817-29. doi: 10.1517/14712598.2013.778969. Epub 2013 Mar 27.

Abstract

Objectives: Bronchopulmonary dysplasia (BPD) is a significant global health problem and currently lacks effective therapy. We established a neonatal rat model of BPD to investigate therapeutic potential of bone marrow-derived mesenchymal stem cells (BMSCs) in neonatal hyperoxic lung injury.

Methods: BMSCs were isolated, identified, and transfected by lentiviral vector carrying green fluorescent protein gene in vitro. Neonatal Sprague-Dawley rats were injected intravenously with either BMSCs or phosphate-buffered saline following 95% oxygen exposure, and assessed for the survival rate and alveolar injury during recovery.

Results: Treatment with BMSCs after oxygen exposure for 7 days improved survival of neonatal rat during recovery. BMSCs protected against neonatal rat hyperoxic lung injury during recovery as demonstrated by enhanced expression of AQP5 and SP-C, likely due to the suppression of alveolar cell apoptosis and lung inflammation responses to oxygen with up-regulation of the expression of BCL-2 gene and down-regulation of the expression of BAX gene and stimulation of vascular endothelial growth factor and so on.

Conclusions: BMSCs protect against O2-mediated injury partially through stimulation of potent mediators that participate in tissue repair.

MeSH terms

  • Animals
  • Animals, Newborn
  • Apoptosis
  • Aquaporin 5 / metabolism
  • Bronchopulmonary Dysplasia / etiology
  • Bronchopulmonary Dysplasia / metabolism
  • Bronchopulmonary Dysplasia / pathology
  • Bronchopulmonary Dysplasia / surgery*
  • Cell Tracking
  • Cells, Cultured
  • Disease Models, Animal
  • Green Fluorescent Proteins / biosynthesis
  • Green Fluorescent Proteins / genetics
  • Hyperoxia / complications*
  • Lung / metabolism
  • Lung / pathology*
  • Mesenchymal Stem Cell Transplantation*
  • Mesenchymal Stem Cells / metabolism
  • Peptides / metabolism
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Time Factors
  • Transfection
  • Vascular Endothelial Growth Factor A / metabolism
  • bcl-2-Associated X Protein / metabolism

Substances

  • Aqp5 protein, rat
  • Aquaporin 5
  • Bax protein, rat
  • Peptides
  • Proto-Oncogene Proteins c-bcl-2
  • Vascular Endothelial Growth Factor A
  • bcl-2-Associated X Protein
  • vascular endothelial growth factor A, rat
  • Sftpc protein, rat
  • Green Fluorescent Proteins