Human mesenchymal stem cells ameliorate experimental pulmonary hypertension induced by maternal inflammation and neonatal hyperoxia in rats
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Chung-Ming Chen1,2, Willie Lin3, Liang-Ti Huang2,4 and Hsiu-Chu Chou5
1Department of Pediatrics, Taipei Medical University Hospital, Taipei, Taiwan
2Department of Pediatrics, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan
3Meridigen Biotech Co., Ltd., Taipei, Taiwan
4Department of Pediatrics, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan
5Department of Anatomy and Cell Biology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan
Hsiu-Chu Chou, email: [email protected]
Keywords: lipopolysaccharide, hyperoxia, pulmonary hypertension, β-myosin heavy chain, toll-like receptor 4
Received: December 05, 2016 Accepted: June 30, 2017 Published: July 19, 2017
Pulmonary hypertension is a critical problem in infants with bronchopulmonary dysplasia. This study determined the therapeutic effects of human mesenchymal stem cells (MSCs) on pulmonary hypertension in an animal model. Pregnant Sprague–Dawley rats were intraperitoneally injected with lipopolysaccharide (LPS, 0.5 mg/kg/day) on gestational days 20 and 21. The pups were randomly assigned to two treatment conditions: room air (RA) or an O2-enriched atmosphere. On postnatal day 5, they were intratracheally transplanted with human MSCs (3 × 105 and 1 × 106 cells) in 0.03 mL of normal saline (NS). Five study groups were examined: normal, LPS+RA+NS, LPS+O2+NS, LPS+O2+MSCs (3 × 105 cells), and LPS+O2+MSCs (1 × 106 cells). On postnatal day 14, the pup lungs and hearts were collected for histological examinations. The LPS+RA+NS and LPS+O2+NS groups exhibited a significantly higher right ventricle (RV):left ventricle (LV) thickness ratio and medial wall thickness (MWT) and higher β-myosin heavy chain (β-MHC) and toll-like receptor (TLR) 4 expression than did the normal group. Human MSC transplantation in LPS- and O2-treated rats reduced the MWT, RV:LV thickness ratio, and β-MHC and TLR4 expression to normal levels. Thus, intratracheal human MSC transplantation ameliorates pulmonary hypertension, probably by suppressing TLR4 expression in newborn rats.
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