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

Abstract

Objective: To study the influence of bone marrow mesenchymal stem cells (MSCs) transplantation on hypoxic pulmonary hypertension (HPH) in rats. Methods: MSCs in SD rats were separated, cultivated, identified in vitro, and labeled by the green fluorescence protein (GFP) adenovirus. Healthy male SD rats were randomly divided into four groups: normal control group (NC group) and HPH group, with eight rats in each group respectively; HPH + mesenchymal stem cell transplantation group (MSCs group) and HPH + vascular endothelial growth factor + mesenchymal stem cell transplantation group (VEGF + MSCs group), with twenty-four rats in each group respectively. In this experiment, intermittent normobaric hypoxia was employed to establish the pulmonary hypertension rat models, with stem cells transfected and transplanted. The mean pulmonary artery pressure (mPAP) was observed in rats to calculate the right ventricular hypertrophy index (RVHI); the morphological changes of pulmonary arterioles in each group of rats were observed under the microscope; the distribution and manifestation of MSCs fluorescently labeled by adenovirus transfection were observed in pulmonary arterioles under the fluorescence microscope at the set time points of 7 d, 14 d and 28 d after the transplantation of stem cells. Results: For NC group, the mPAP (mmHg) was 15.5 ± 1.5 at 28 d, while the mPAP in HPH, MSCs and VEGF + MSCs groups were 26.1 ± 1.9, 21.6 ± 2.7 and 20.1 ± 2.9 respectively which were apparently higher than that in NC group ( p < .01). Compared with HPH group ( p < .01), the mPAP was obviously decreased in MSCs and VEGF + MSCs groups. There was no significant difference between MSCs and VEGF + MSCs groups. At 28 d, RVHI for NC group was 0.28 ± 0.02, while the RVHI in HPH, MSCs and VEGF + MSCs groups were 0.43 ± 0.07, 0.34 ± 0.03 and 0.35 ± 0.01 respectively which were apparently higher than that in NC group ( p < .01). In comparison with HPH group, RVHI was significantly decreased in MSCs and VEGF + MSCs groups ( p < .05). There was no significant difference between MSCs and VEGF + MSCs groups. For HPH group, at 28 d, pulmonary arterioles were apparently thickened, with luminal stenosis & obliteration and incomplete endothelial cells. Compared with HPH group, pulmonary arterioles in MSCs group became thinning, with the lumen unobstructed and the integrity of endothelial cells improved. The changes in the manifestation of MSCs and VEGF + MSCs groups were not significant. Conclusions: The transplantation of MSCs can improve the remodeling of pulmonary arterioles to partially reverse the progress of HPH; the combined transplantation of VEGF and MSCs doesn’t improve the effect of MSC transplantation.