TY - JOUR
T1 - Human mesenchymal stem cells ameliorate experimental pulmonary hypertension induced by maternal inflammation and neonatal hyperoxia in rats
AU - Chen, Chung Ming
AU - Lin, Willie
AU - Huang, Liang Ti
AU - Chou, Hsiu Chu
N1 - Publisher Copyright:
© Chen et al.
PY - 2017
Y1 - 2017
N2 - 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.
AB - 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.
KW - Hyperoxia
KW - Lipopolysaccharide
KW - Pulmonary hypertension
KW - Toll-like receptor 4
KW - β-myosin heavy chain
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U2 - 10.18632/oncotarget.19388
DO - 10.18632/oncotarget.19388
M3 - Article
AN - SCOPUS:85030862949
SN - 1949-2553
VL - 8
SP - 82366
EP - 82375
JO - Oncotarget
JF - Oncotarget
IS - 47
ER -