Allogeneic bone marrow mesenchymal stem cells transplantation has therapeutic effect on pulmonary arterial hypertension in rats

Objective To explore the mechanisms and therapeutic effect of bone marrow-derived mesenchymal stem cells(MSCs) on rat models with pulmonary arterial hypertension(PAH).Methods MSCs were obtained from bone marrow of Sprague-Dawley(SD) rats,and were separated,cultured,purified and propagated in vitro.Healthy male SD rats were randomly divided into 3 groups,normal control group(n = 15),PAH model group(n = 30),MSCs transplanted group(n = 20).The rats of the PAH model group and MSCs transplanted group were injected with a single subcutaneous monocrotaline(50 mg/kg) to induce the models of PAH.Rats of the three groups were fed under the same condition.After 3 weeks,MSCs were signed by Hoechst 33342.Then 5 × 106 MSCs cultured in 1 ml phosphate-buffered saline was infused into the rats in MSCs transplanted group by sublingual vein.The same dose of L-DMEM was also injected in PAH model group.Mean pulmonary arterial pressure,right ventricle hypertrophy index,blood gas analysis and the microstructure changes of small pulmonary vascular were checked and observed on day 28.Results When the MSCs were transplanted into the rats with PAH after 28 days,the survival rate of MSCs transplanted group is 100% and the mean pulmonary arterial pressure decreased obviously,right ventricle hypertrophy index degraded too,the results of blood gas analysis and the pulmonary arteries remodeling,were improved significantly in MSCs transplanted group.The changes were better than that in PAH model group with statistical significance(P 0.01).MSCs labelled Hoechst 33342 were observed to permanently planted and differentiated into plentiful collateral circulations in lungs by fluorescence microscope.The pulmonary arteries remodeling was attenuated obviously in MSCs transplanted group.Conclusions These results indicated that MSCs transplantation can reduce and reverse the progression of PAH.The possible mechanism is that MSCs cells can repair the monocrotaline-damaged lungs by collateral circulation formation,retroconversion vascular remodeling.