Human mesenchymal stem cells ameliorate experimental pulmonary hypertension induced by maternal inflammation and neonatal hyperoxia in rats

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 O-2-enriched atmosphere. On postnatal day 5, they were intratracheally transplanted with human MSCs (3 x 10(5) and 1 x 10(6) cells) in 0.03 mL of normal saline (NS). Five study groups were examined: normal, LPS+RA+NS, LPS+O-2+NS, LPS+O-2+MSCs (3 x 10(5) cells), and LPS+O-2+MSCs (1 x 10(6) cells). On postnatal day 14, the pup lungs and hearts were collected for histological examinations. The LPS+RA+NS and LPS+O-2+NS groups exhibited a significantly higher right ventricle (RV): left ventricle (LV) thickness ratio and medial wall thickness (MWT) and higher beta-myosin heavy chain (beta-MHC) and toll-like receptor (TLR) 4 expression than did the normal group. Human MSC transplantation in LPS-and O-2-treated rats reduced the MWT, RV: LV thickness ratio, and beta-MHC and TLR4 expression to normal levels. Thus, intratracheal human MSC transplantation ameliorates pulmonary hypertension, probably by suppressing TLR4 expression in newborn rats.