Role of bone marrow mesenchymal stem cells transplantation in treatment of pulmonary arterial hypertension in rats carrying hepatocyte growth factor

Objective To study the role of bone marrow mesenchymal stem cells(MSCs) transplantation in treatment of monocrotaline(MCT)-induced pulmonary arterial hypertension(PAH) in rats carrying hepatocyte growth factor(HGF) and its mechanism. Methods MSC isolated from bone marrow of 3-week old male SD rats were incubated in vitro with adhesion culture method,purified and transfected with adenovirus(Ad)-mediated HGF.The rats were randomly divided into PAH group,MSC transplantation group,and Ad-mediated HGF transplantation group,10 in each group.After a PAH model was established by intraperitoneal injection of monocrotaline(MCT) at the dose of 60mg/kg,1ml L-DMEM was injected into the jugular vein of rats in PAH group,1ml suspension containing 5×10⁶ MSC transfected with empty adenovirus vector was injected into rats of HGF transplantation group.Hemodynamics,RV/LV and plasma ET-1 level in rats of different groups were observed. Results No significant difference was found in BP among different groups 3 weeks after treatment of PAH(pulmonary arterial hypertension).The PASP(pulmonary artery systdic pressure) and mPAP(mean pulmonary arterial pressure) were significantly lower in Ad-mediated HGF transplantation group than in PAH group and MSCs transplantation group(37.227 2±5.381 60 vs 45.069 0±7.177 97 and 44.142 0±6.673 75,25.693 5± 1.446 33 vs 30.800 2±1.256 15 and 30.359 1±1.172 52,P<0.05).No significant difference was found in RV/LV among Ad-mediated HGF transplantation group,PAH group and MSCs transplantation group(42.200 0±8.060 59,46.858 0±8.241 61,46.750 0±10.420 14, P>0.05)although it was decreased.The plasma ET-1 level was significantly lower in Ad-mediated HGF transplantation group than in PAH group and MSC transplantation group(23.862 70±7.426 76 vs 28.372 0±4.402 75 and 31.849 0±7.547 13,P<0.05). Conclusion MSC carrying HGF transplantation therapy can significantly reduce the PASP and mPAP,improve hemodynamics,delay and even reverse right ventricular hypertrophy,and decrease plasma ET-1 level in rats with PAH,thus protecting vascular endothelium cells against damage and blood vessels against constriction.