The effect of bone marrow mesenchymal stem cell transplantation on hypoxic pulmonary hypertension in rats

OBJECTIVE: To study the influence of bone marrow mesenchymal stem cells (MSCs) transplantation on hypoxic pulmonary hypertension (HPH) in rats. METHODS: SD rats MSCs were separated, cultivated, identified and labeled by the green fluorescence protein (GFP) gene virus and transplanted in vitro. Healthy male SD rats were randomly divided into four groups: Normal control group (NC group) and HPH group (eight rats respectively), HPH+ MSCs transplantation group and HPH+ VEGF+ MSCs transplantation group (twenty-four respectively). The test employed atmospheric intermittent low oxygen method to establish the rat model of pulmonary hypertension and stem cells were transferred and transplanted. The rats' mean pulmonary artery pressure (mPAP) was observed; right ventricular hypertrophy index (RVHI) was calculated; the morphological change of lung small artery in various groups of rats was observed under the microscope; the distribution of lung small artery and adenovirus transfection fluorescently labeled MSCs was observed under a fluorescent microscope after 7, 14 and 28 days when stem cell was transplanted. RESULTS: For NC group, the mPAP (mmHg) was 15.5 +/- 1.5 after twenty-eight days while the mPAPs for HPH , MSCs and MSCs+ VEGF were 26.1 +/- 1.9, 21.6 +/- 2.7 and 20.1 +/- 2.9 respectively which were apparently higher than that of NC group (P < 0.01) and compared with HPH group (P < 0.01), which declined clearly. There was no significant difference between MSCs and MSCs+ VEGF. After twenty-eight days, RVHI for NC group was 0.28 +/- 0.02 while the RVHI for HPH, MSCs and MSCs + VEGF were 0.43 +/- 0.07, 0.34 +/- 0.03 and 0.35 +/- 0.01 respectively which was apparently higher than that of NC group (P < 0.01) but which was clearly lower than that of MSCs and MSCs+ VEGF (P < 0.05) and there was no significant difference between MSCs and MSCs + VEGF. For HPH group, pulmonary arteriole wall became apparently thicker, the lumen became significantly narrow and nearly obstructed after twenty-eight days, the endothelial cells were incomplete; compared with HPH group, pulmonary arteriole wall of MSCs group became thin, the lumen was smooth and the completeness of endothelial cells was improved. Whereas for MSCs and MSCs + VEGF, these changes were not significantly clear. CONCLUSION: After MSCs transplantation, mPAP and RVHI decline sharply and lung small artery remodeling is improved which partially reverses HPH process; there is no significant difference between VEGF together with MSCs transplantation group and pure MSCs.