Umbilical cord blood mesenchymal stem cell transplantation in treatment of pulmonary hypertension in rats

AIM: To establish a pulmonary arterial hypertension(PAH) animal model by arterial-vein shunting by combining with injection of monocrotaline(MCT) and to observe the therapeutic effects of mesenchymal stem cells(MSCs) from umbilical cord blood on PAH in Sprague Dawley(SD) rats.METHODS: For establishment of the animal model,60 healthy male SD rats were randomly divided into four groups: 1)normal control group(n=15): rats were given no treatment;2)A-VF+MCT group(n=15): rats were given a single s.c.injection of crotaline(50 mg/kg) after the A-VF operation to establish the PAH model;3)A-VF+MCT+MSCs group: 5×106 MSCs labeled with Hoechst 33342 were injected into rats through the tail vein 4 weeks after the shunting operation;4)A-VF+MCT+DMEM/F12 group: rats were injected a single s.c.cell culture medium 4 weeks after the shunting operation.Mean pulmonary arterial pressure(mPAP),right ventricle index(RVHI) and the microstructure and remodeling changes of small pulmonary vessels were determined 4 weeks after MSC transplantation.RESULTS: Compared with the normal control group,the PAH SD rat model was successfully established after 4 weeks of the A-VF+MCT method.Eight weeks after A-VF+MCT,mPAP and right ventricle index(RVI) were significantly enhanced,and pulmonary artery tunica media and right ventricular wall significantly thickened.The mPAP,RV/(LV+S),MT% and MA% decreased significantly in transplantation group compared to A-VF+MCT group(P<0.01).The mortality rate of PAH rats decreased from 66.7% to 13.3%.Fluorescence microscopy showed that MSCs labeled with Hoechst 33342 were permanently implanted in the tunica intima of the lung.CONCLUSION: MSC transplantation can significantly reduce pulmonary arterial pressure,alleviate pulmonary arterial remodeling,and lower the mortality rate of rats with PAH.