Mesenchymal Stromal Cell-derived Exosomes Attenuate Experimental Pulmonary Arterial Hypertension

Background: Pulmonary arterial hypertension (PH) is a chronic disease that ultimately progresses to right ventricular failure and death, until now there is still lack of effective treatment applied. The purpose of the present study was to observe the protective effect of mesenchymal stromal cell derived exosomes (MSC-EXO) against experimental pulmonary arterial hypertension (PH) and right ventricular failure. Methods: All the experimental rats received an intraperitoneal injection of 50 mg/kg monocrotaline to induce PH model. Three weeks after the model was successfully established, the cell Culture Media (CM) or MSC-EXO derived from human umbilical cord was administered daily via the tail vein. All animals were randomly divided into 4 groups: Control (saline-treated), MCT-PH, MCT-CM and MCT-EXO groups. Post-operation, hemodynamic data and index of right ventricular hypertrophy (RVHI) were recorded to evaluate the inhibition of MSC-EXO on MCT-induced PH. Histology, immunohistochemistry and western blot were used to analyze the effect of MSC-EXO against vascular remodeling and further reveal the mechanism. Results: In the present study, our results showed that MSC-EXO administration could significantly reduce the right ventricular systolic pressure (RVSP) and RVHI, suppress the pulmonary vascular remodeling and the endothelialmesenchymal transition (EndMT) process. Conclusion: Our results provided the firm information for a new method in treatment of PH, the mechanism may be may be related with the inhibition of vascular remodeling and EndMT.