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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 (3×10(5) and 1×10(6) 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 (3×10(5) cells), LPS+RA+MSC (1×10(6) cells), LPS+O2+NS, LPS+O2+MSC (3×10(5) cells), and LPS+O2+MSC (1×10(6) 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.

journal_name

Am J Transl Res

journal_title

American journal of translational research

authors

Chou HC,Li YT,Chen CM

subject

Has Abstract

pub_date

2016-02-15 00:00:00

pages

342-53

issue

issn

1943-8141

journal_volume

pub_type

杂志文章

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