Abstract 16849: Extracellular Vesicles Derived From Mesenchymal Stem Cells Protects Mice From Monocrotaline-Induced Pulmonary Hypertension and Improve Echocardiographic Parameters

Abstract

Introduction: Pulmonary hypertension (PH) is a currently incurable disease with high morbidity and mortality. Treatment with extracellular vesicles derived from mesenchymal stem cells (MSC-EVs) appeared to be effective and promising. Objective: We aimed at evaluating whether MSC-EVs could improve right ventricle (RV) and pulmonary artery (PA) functions in mice with PAH induced by monocrotaline (MCT). Methods: FVB mice (M/F – 6 weeks) received MCT injections 1x/week for 4 weeks (60mg/kg sc.) and were treated with MSCs-EVs 24 hours after each MCT injection (3x10 6 cells in 100μL PBS 1x, iv.). The experimental groups were: Control (vehicle-vehicle; n=9); MCT (MCT-vehicle; n=10); Control EVs (vehicle-EVs; n=8); MCT EVs (MCT-EVs; n=10); PA acceleration time (PAT), PA ejection time (PET) and tricuspid annular plane systolic excursion (TAPSE) were assessed by echocardiography 28 days after first MCT injection; Fulton index was used to calculate RV hypertrophy, and pulmonary vascular remodeling (WT/D) was assessed by histology. Results: PAT and PAT/PET were decreased by 22.6±5.7% and 15.6±4.9%, respectively, in MCT group compared to Control (p<0.01 and p<0.02). PAT was increased in Control EVs and MCT EVs groups when compared with MCT group (by 28.2±7.6%, p<0.01 and 20±6.9%, p<0.04, respectively). TAPSE (figure 1) was decreased in the MCT group compared with Control (42.9±6.7%, p<0.0001) and increased in both Control EVs (62.8±12.2%, p<0.0001) and MCT EVs (52.7±11.1%, p<0.0005) groups compared with MCT group. In addition, MCT group presented RV hypertrophy 49.4±16.5% higher than Control (p<0.03), and 29.1±10.4% higher than MCT EVs group (p<0.05). The WT/D was increased in MCT compared to Control (63.7±7.6%, p<0.0001), but decreased in Control EVs (44.9±4.6%, p<0.0001) and MCT EVs (44.3±5.4%, p<0.0001) in relation to MCT group. Conclusion: Treatment with MSC-EVs protects against the development of PH and improves PA and the RV function in MCT-treated mice.