Monday, March 8, 2010

Therapeutic Effect of Bone Marrow Mesenchymal Stem Cells to Experimental Pulmonary Arterial Hypertension in Rats

Therapeutic Effect of Bone Marrow Mesenchymal Stem Cells to Experimental Pulmonary Arterial  Hypertension in Rats
    [Key words] hypertension,pulmonary; mesenchymal stem cells; blood gas analysis; hemodynamics
     To explore the change of hemodynamic parameter in bone marrow mesenchymal stem cells(MMSCs) transplantation to treat the experimental pulmonary arterial  hypertension (PAH) in rats. Method: MMSCs cells were collected from bone marrow of SD rat's femoral and tibial bones,cultured and passaged in vitro,then purified by density gradient centrifugation and adhesive-screening method.60 healthy male Sprague-Dawleye rats(mean weighing 180±5 g) were randomly divided into 3 groups: normal control group (group C), MMSCs transplanted group(group M), PAH model group (group H ).The rats of the two latter group were given a single subcutaneous crotaline(50 mg/kg) to make the model of PAH. The rats of normal control group were injected respectively a single subcutaneous 0.9%NaCL(6 ml/kg).The three groups were fed in the same condition.After 3 weeks, 5×106 MMSCs cultured in l ml phosphate-buffered saline were infused into the rats respectively in group M  by sublingual vein and 1 ml L-DMEM was did in group H .The index of right ventricle systolic pressure(RVSP),right ventricle hypertrophy index, arterial blood gas analysis and the changes of small pulmonary blood vessel were observed after 28 day.Results: The administration of MMSCs 28 days after PAH the percent of viability is 100 in transplanted group, and it nearly completely prevented the increase in right ventricular systolic pressure(RVSP)with PAH alone (32.20±2.32 versus 48.30±1.56 mm Hg, respectively P<0.05),right ventricle hypertrophy index degraded too(38.80±3.24% versus 45.10±3.43 %, respectively P<0.05 ), and relative media thickness(MT) decreased obviously but the VA% raised, results of Blood gas analysis such as pH、PaO2、HCO3- degraded significantly. MMSCs labeled Hoechst 33342 were observed that they can permanent planted and differentiated into plentiful collateral circulations in lung by fluorescence microscope . The pulmonary arteries remodeling was attenuated effecfively in MSCs transplanted group. Conclusions: These results indicated that bone marrow–derived Mesenchymal stem cells (MMSCs) could reduce and even  reversion the progression of Pulmonary arterial hypertension (PAH) induced by crotaline.The heart function and hemodynamic parameter had obvious improved.