Exosomes from mesenchymal stem cells prevented and reversed monocrotaline-induced pulmonary hypertension in mice, likely due to their anti-inflammatory and anti-proliferative microRNA cargo.
Do mesenchymal stem cell-derived exosomes prevent or reverse monocrotaline-induced pulmonary hypertension in mice?
Mesenchymal stem cell-derived exosomes can prevent and reverse monocrotaline-induced pulmonary hypertension in mice, likely due to their anti-inflammatory and anti-proliferative microRNA cargo.
AIMS: Extracellular vesicles (EVs) from mice with monocrotaline (MCT)-induced pulmonary hypertension (PH) induce PH in healthy mice, and the exosomes (EXO) fraction of EVs from mesenchymal stem cells (MSCs) can blunt the development of hypoxic PH. We sought to determine whether the EXO fraction of EVs is responsible for modulating pulmonary vascular responses and whether differences in EXO-miR content explains the differential effects of EXOs from MSCs and mice with MCT-PH. METHODS AND RESULTS: Plasma, lung EVs from MCT-PH, and control mice were divided into EXO (exosome), microvesicle (MV) fractions and injected into healthy mice. EVs from MSCs were divided into EXO, MV fractions and injected into MCT-treated mice. PH was assessed by right ventricle-to-left ventricle + septum (RV/LV + S) ratio and pulmonary arterial wall thickness-to-diameter (WT/D) ratio. miR microarray analyses were also performed on all EXO populations. EXOs but not MVs from MCT-injured mice increased RV/LV + S, WT/D ratios in healthy mice. MSC-EXOs prevented any increase in RV/LV + S, WT/D ratios when given at the time of MCT injection and reversed the increase in these ratios when given after MCT administration. EXOs from MCT-injured mice and patients with idiopathic pulmonary arterial hypertension (IPAH) contained increased levels of miRs-19b,-20a,-20b, and -145, whereas miRs isolated from MSC-EXOs had increased levels of anti-inflammatory, anti-proliferative miRs including miRs-34a,-122,-124, and -127. CONCLUSION: These findings suggest that circulating or MSC-EXOs may modulate pulmonary hypertensive effects based on their miR cargo. The ability of MSC-EXOs to reverse MCT-PH offers a promising potential target for new PAH therapies.
Aliotta et al. (Mon,) conducted a other in Pulmonary hypertension. Exosomes (EXO) from MCT-injured mice or MSCs vs. Microvesicles (MV) or control was evaluated on Right ventricle-to-left ventricle + septum (RV/LV + S) ratio and pulmonary arterial wall thickness-to-diameter (WT/D) ratio. Exosomes from mesenchymal stem cells prevented and reversed monocrotaline-induced pulmonary hypertension in mice, likely due to their anti-inflammatory and anti-proliferative microRNA cargo.