Mesenchymal stem cells in combination with erythropoietin repair hyperoxia-induced alveoli dysplasia injury in neonatal mice via inhibition of TGF-β1 signaling

Oncotarget. 2016 Jul 26;7(30):47082-47094. doi: 10.18632/oncotarget.9314.

Abstract

The aim of the present study is to investigate the protection effects of bone marrow mesenchymal stem cells (MSCs) in combination with EPO against hyperoxia-induced bronchopulmonary dysplasia (BPD) injury in neonatal mice. BPD model was prepared by continuous high oxygen exposure, 1×106 bone marrow MSCs and 5000U/kg recombinant human erythropoietin (EPO) were injected respectively. Results showed that administration of MSCs, EPO especially MSCs+EPO significant attenuated hyperoxia-induced lung damage with a decrease of fibrosis, radical alveolar counts and inhibition of the occurrence of epithelial-mesenchymal transition (EMT). Furthermore, MSCs+EPO co-treatment more significantly suppressed the levels of transforming growth factor-β1(TGF-β1) than MSCs or EPO alone. Collectively, these results suggested that MSCs, EPO in particular MSCs+EPO co-treatment could promote lung repair in hyperoxia-induced alveoli dysplasia injury via inhibition of TGF-β1 signaling pathway to further suppress EMT process and may be a promising therapeutic strategy.

Keywords: BPD; EPO; ETM; MSCs; TGF-β1.

MeSH terms

  • Animals
  • Bronchopulmonary Dysplasia / etiology
  • Bronchopulmonary Dysplasia / therapy*
  • Cells, Cultured
  • Combined Modality Therapy / methods
  • Disease Models, Animal
  • Epithelial-Mesenchymal Transition / drug effects
  • Erythropoietin / therapeutic use*
  • Female
  • Fibrosis / drug therapy
  • Humans
  • Hyperoxia / complications
  • Mesenchymal Stem Cell Transplantation*
  • Mice
  • Mice, Inbred C57BL
  • Pulmonary Alveoli / drug effects
  • Pulmonary Alveoli / pathology*
  • Recombinant Proteins / therapeutic use
  • Signal Transduction / drug effects
  • Transforming Growth Factor beta1 / metabolism*

Substances

  • EPO protein, human
  • Recombinant Proteins
  • Transforming Growth Factor beta1
  • Erythropoietin