Therapeutic effects of mesenchymal stem cell-derived microvesicles on pulmonary arterial hypertension in rats  

作　　者：Jian-ying CHEN Ran AN Zhen-jun LIU Jin-ju WANG Shu-zhen CHEN Mian-ming HONG Jing-hu LIU Meng-yuan XIAO Yan-fang CHEN 

机构地区：[1]Department of Cardiology, the Affiliated Hospital of Guangdong Medical College, Zhanjiang 524001, China [2]Department of Pharma-cology and Toxicology, Boonshoft School of Medicine, Wright State University, Dayton, OH 45435, USA

出　　处：《Acta Pharmacologica Sinica》2014年第9期1121-1128,共8页中国药理学报（英文版）

摘　　要：Aim： Microvesicles （MVs） are nanoscale membrane fragments released from virtually all cell types upon activation or apoptosis, and may contribute to the beneficial effects of stem cell therapy. In this study, we investigated the therapeutic effects of mesenchymal stem cell （MSC） derived MVs （MSC-MVs） on pulmonary artery hypertension （PAH） in rats. Methods： MSC-MVs were isolated from rat bone marrow MSCs that were cultured in a serum-free conditioned medium. Transmission electron microscopy （TEM）, flow cytometry and nanoparticle tracking analysis （NTA） were used to characterize the MVs. Adult SD rats were injected with monocrotaline （50 mg/kg, sc） to induce PAH. Three weeks later, the rats were intravenously injected with MSCs, MSC-MVs or saline for 2 weeks. At the end of treatments, the hemodynamic parameters and pathological right ventricular and pulmonary arterial remodeling were analyzed in each group. Results： The MSC-MVs showed general morphologic characteristics of MVs and expressed annexin V and CD29 markers under TEM, and their size ranged from 40 to 300 nm. Intravenous injection of MSC-MVs or MSCs significantly ameliorated the mean pulmonary artery pressure （mPAP） and mean right ventricle pressure （mRVP） in PAH rats. Furthermore, intravenous injection of MSC-MVs or MSCs significantly decreased the right ventricle （RV） hypertrophy and pulmonary arteriole area index （AI） and thickness index （TI） in PAH rats. Conclusion： Intravenous injection of MSC-MVs or MSCs produces similar beneficial effects for treating PAH, and our results provide a basis for cell-free approach in stem cell therapy.Aim： Microvesicles （MVs） are nanoscale membrane fragments released from virtually all cell types upon activation or apoptosis, and may contribute to the beneficial effects of stem cell therapy. In this study, we investigated the therapeutic effects of mesenchymal stem cell （MSC） derived MVs （MSC-MVs） on pulmonary artery hypertension （PAH） in rats. Methods： MSC-MVs were isolated from rat bone marrow MSCs that were cultured in a serum-free conditioned medium. Transmission electron microscopy （TEM）, flow cytometry and nanoparticle tracking analysis （NTA） were used to characterize the MVs. Adult SD rats were injected with monocrotaline （50 mg/kg, sc） to induce PAH. Three weeks later, the rats were intravenously injected with MSCs, MSC-MVs or saline for 2 weeks. At the end of treatments, the hemodynamic parameters and pathological right ventricular and pulmonary arterial remodeling were analyzed in each group. Results： The MSC-MVs showed general morphologic characteristics of MVs and expressed annexin V and CD29 markers under TEM, and their size ranged from 40 to 300 nm. Intravenous injection of MSC-MVs or MSCs significantly ameliorated the mean pulmonary artery pressure （mPAP） and mean right ventricle pressure （mRVP） in PAH rats. Furthermore, intravenous injection of MSC-MVs or MSCs significantly decreased the right ventricle （RV） hypertrophy and pulmonary arteriole area index （AI） and thickness index （TI） in PAH rats. Conclusion： Intravenous injection of MSC-MVs or MSCs produces similar beneficial effects for treating PAH, and our results provide a basis for cell-free approach in stem cell therapy.

关 键 词：stem cell therapy bone marrow mesenchymal stem cell MICROVESICLE pulmonary artery hypertension chronic heart disease 

分 类 号：S858.31[农业科学—临床兽医学] Q254[农业科学—兽医学]