Human mesenchymal stem cells attenuate experimental bronchopulmonary dysplasia induced by perinatal inflammation and hyperoxia

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Abstract

Background: Systemic maternal inflammation and neonatal hyperoxia arrest alveolarization in neonates. The aims were to test whether human mesenchymal stem cells (MSCs) reduce lung inflammation and improve lung development in perinatal inflammation- and hyperoxia-induced experimental bronchopulmonary dysplasia. Methods: Pregnant Sprague-Dawley rats were intraperitoneally injected with lipopolysaccharide (LPS, 0.5 mg/kg/ day) on Gestational Days 20 and 21. Human MSCs (3×105 and 1×106 cells) in 0.03 ml normal saline (NS) were administered intratracheally on Postnatal Day 5. Pups were reared in room air (RA) or an oxygen-enriched atmosphere (O2) from Postnatal Days 1 to 14, and six study groups were obtained: LPS+RA+NS, LPS+RA+MSC (3×105 cells), LPS+RA+MSC (1×106 cells), LPS+O2+NS, LPS+O2+MSC (3×105 cells), and LPS+O2+MSC (1×106 cells). The lungs were excised for cytokine, vascular endothelial growth factor (VEGF) and connective tissue growth factor (CTGF) expression, and histological analyses on Postnatal Day 14. Results: Body weight was significantly lower in rats reared in hyperoxia than in those reared in RA. The LPS+O2+NS group exhibited a significantly higher mean linear intercept (MLI) and collagen density and a significantly lower vascular density than the LPS+RA+NS group did. Administering MSC to hyperoxia-exposed rats improved MLI and vascular density and reduced tumor necrosis factor-α and interleukin- 6 levels and collagen density to normoxic levels. This improvement in lung development and fibrosis was accompanied by an increase and decrease in lung VEGF and CTGF expression, respectively. Conclusion: Human MSCs attenuated perinatal inflammation- and hyperoxia-induced defective alveolarization and angiogenesis and reduced lung fibrosis, likely through increased VEGF and decreased CTGF expression.

Original languageEnglish
Pages (from-to)342-353
Number of pages12
JournalAmerican Journal of Translational Research
Volume8
Issue number2
Publication statusPublished - 2016

Fingerprint

Bronchopulmonary Dysplasia
Hyperoxia
Stem cells
Mesenchymal Stromal Cells
Inflammation
Air
Connective Tissue Growth Factor
Lung
Vascular Endothelial Growth Factor A
Rats
Blood Vessels
Fibrosis
Collagen
Atmosphere
Sprague Dawley Rats
Lipopolysaccharides
Interleukin-6
Pneumonia
Tumor Necrosis Factor-alpha
Body Weight

Keywords

  • Connective tissue growth factor
  • Hyperoxia
  • Lipopolysaccharide
  • Mesenchymal stem cells
  • Vascular endothelial growth factor

ASJC Scopus subject areas

  • Medicine(all)
  • Cancer Research
  • Clinical Biochemistry
  • Molecular Medicine

Cite this

@article{4ab83a5845b94f4d8b36ffdc900fd891,
title = "Human mesenchymal stem cells attenuate experimental bronchopulmonary dysplasia induced by perinatal inflammation and hyperoxia",
abstract = "Background: Systemic maternal inflammation and neonatal hyperoxia arrest alveolarization in neonates. The aims were to test whether human mesenchymal stem cells (MSCs) reduce lung inflammation and improve lung development in perinatal inflammation- and hyperoxia-induced experimental bronchopulmonary dysplasia. Methods: Pregnant Sprague-Dawley rats were intraperitoneally injected with lipopolysaccharide (LPS, 0.5 mg/kg/ day) on Gestational Days 20 and 21. Human MSCs (3×105 and 1×106 cells) in 0.03 ml normal saline (NS) were administered intratracheally on Postnatal Day 5. Pups were reared in room air (RA) or an oxygen-enriched atmosphere (O2) from Postnatal Days 1 to 14, and six study groups were obtained: LPS+RA+NS, LPS+RA+MSC (3×105 cells), LPS+RA+MSC (1×106 cells), LPS+O2+NS, LPS+O2+MSC (3×105 cells), and LPS+O2+MSC (1×106 cells). The lungs were excised for cytokine, vascular endothelial growth factor (VEGF) and connective tissue growth factor (CTGF) expression, and histological analyses on Postnatal Day 14. Results: Body weight was significantly lower in rats reared in hyperoxia than in those reared in RA. The LPS+O2+NS group exhibited a significantly higher mean linear intercept (MLI) and collagen density and a significantly lower vascular density than the LPS+RA+NS group did. Administering MSC to hyperoxia-exposed rats improved MLI and vascular density and reduced tumor necrosis factor-α and interleukin- 6 levels and collagen density to normoxic levels. This improvement in lung development and fibrosis was accompanied by an increase and decrease in lung VEGF and CTGF expression, respectively. Conclusion: Human MSCs attenuated perinatal inflammation- and hyperoxia-induced defective alveolarization and angiogenesis and reduced lung fibrosis, likely through increased VEGF and decreased CTGF expression.",
keywords = "Connective tissue growth factor, Hyperoxia, Lipopolysaccharide, Mesenchymal stem cells, Vascular endothelial growth factor",
author = "Chou, {Hsiu Chu} and Li, {Yuan Tsung} and Chen, {Chung Ming}",
year = "2016",
language = "English",
volume = "8",
pages = "342--353",
journal = "American Journal of Translational Research",
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T1 - Human mesenchymal stem cells attenuate experimental bronchopulmonary dysplasia induced by perinatal inflammation and hyperoxia

AU - Chou, Hsiu Chu

AU - Li, Yuan Tsung

AU - Chen, Chung Ming

PY - 2016

Y1 - 2016

N2 - Background: Systemic maternal inflammation and neonatal hyperoxia arrest alveolarization in neonates. The aims were to test whether human mesenchymal stem cells (MSCs) reduce lung inflammation and improve lung development in perinatal inflammation- and hyperoxia-induced experimental bronchopulmonary dysplasia. Methods: Pregnant Sprague-Dawley rats were intraperitoneally injected with lipopolysaccharide (LPS, 0.5 mg/kg/ day) on Gestational Days 20 and 21. Human MSCs (3×105 and 1×106 cells) in 0.03 ml normal saline (NS) were administered intratracheally on Postnatal Day 5. Pups were reared in room air (RA) or an oxygen-enriched atmosphere (O2) from Postnatal Days 1 to 14, and six study groups were obtained: LPS+RA+NS, LPS+RA+MSC (3×105 cells), LPS+RA+MSC (1×106 cells), LPS+O2+NS, LPS+O2+MSC (3×105 cells), and LPS+O2+MSC (1×106 cells). The lungs were excised for cytokine, vascular endothelial growth factor (VEGF) and connective tissue growth factor (CTGF) expression, and histological analyses on Postnatal Day 14. Results: Body weight was significantly lower in rats reared in hyperoxia than in those reared in RA. The LPS+O2+NS group exhibited a significantly higher mean linear intercept (MLI) and collagen density and a significantly lower vascular density than the LPS+RA+NS group did. Administering MSC to hyperoxia-exposed rats improved MLI and vascular density and reduced tumor necrosis factor-α and interleukin- 6 levels and collagen density to normoxic levels. This improvement in lung development and fibrosis was accompanied by an increase and decrease in lung VEGF and CTGF expression, respectively. Conclusion: Human MSCs attenuated perinatal inflammation- and hyperoxia-induced defective alveolarization and angiogenesis and reduced lung fibrosis, likely through increased VEGF and decreased CTGF expression.

AB - Background: Systemic maternal inflammation and neonatal hyperoxia arrest alveolarization in neonates. The aims were to test whether human mesenchymal stem cells (MSCs) reduce lung inflammation and improve lung development in perinatal inflammation- and hyperoxia-induced experimental bronchopulmonary dysplasia. Methods: Pregnant Sprague-Dawley rats were intraperitoneally injected with lipopolysaccharide (LPS, 0.5 mg/kg/ day) on Gestational Days 20 and 21. Human MSCs (3×105 and 1×106 cells) in 0.03 ml normal saline (NS) were administered intratracheally on Postnatal Day 5. Pups were reared in room air (RA) or an oxygen-enriched atmosphere (O2) from Postnatal Days 1 to 14, and six study groups were obtained: LPS+RA+NS, LPS+RA+MSC (3×105 cells), LPS+RA+MSC (1×106 cells), LPS+O2+NS, LPS+O2+MSC (3×105 cells), and LPS+O2+MSC (1×106 cells). The lungs were excised for cytokine, vascular endothelial growth factor (VEGF) and connective tissue growth factor (CTGF) expression, and histological analyses on Postnatal Day 14. Results: Body weight was significantly lower in rats reared in hyperoxia than in those reared in RA. The LPS+O2+NS group exhibited a significantly higher mean linear intercept (MLI) and collagen density and a significantly lower vascular density than the LPS+RA+NS group did. Administering MSC to hyperoxia-exposed rats improved MLI and vascular density and reduced tumor necrosis factor-α and interleukin- 6 levels and collagen density to normoxic levels. This improvement in lung development and fibrosis was accompanied by an increase and decrease in lung VEGF and CTGF expression, respectively. Conclusion: Human MSCs attenuated perinatal inflammation- and hyperoxia-induced defective alveolarization and angiogenesis and reduced lung fibrosis, likely through increased VEGF and decreased CTGF expression.

KW - Connective tissue growth factor

KW - Hyperoxia

KW - Lipopolysaccharide

KW - Mesenchymal stem cells

KW - Vascular endothelial growth factor

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