Beneficial Effects of Mesenchymal Stem Cell Delivery via a Novel Cardiac Bioscaffold on Right Ventricles of Pulmonary Arterial Hypertensive Rats

Right ventricular failure (RVF) is a common cause of death in patients suffering from pulmonary arterial hypertension (PAH). The current treatment for PAH only moderately improves symptoms and RVF ultimately occurs. Therefore, it is necessary to develop new treatment strategies to protect against RV maladaptation despite PAH progression. In this study, we hypothesize that local mesenchymal stem cell (MSC) delivery via a novel bioscaffold can improve RV function despite persistent PAH. To test our hypothesis, we induced PAH in adult rats with SU5416 and chronic hypoxia exposure, treated with rat MSCs delivered by intravenous injection, intramyocardial injection or epicardial placement of a bioscaffold, and then examined treatment effectiveness by in vivo pressure-volume measurement, echocardiography, histology and immunohistochemistry. Our results showed that compared to other treatment groups, only the MSC-seeded bioscaffold group resulted in RV functional improvement including restored stroke volume, cardiac output and improved stroke work. Diastolic function indicated by end-diastolic pressure-volume relationship (EDPVR) was improved by the local MSC treatments or bioscaffold alone. Cardiomyocyte hypertrophy and RV fibrosis were both reduced, and von Willebrand Factor expression was restored by the MSC-seeded bioscaffold treatment. Overall, our study suggests a potential new regenerative therapy to rescue the pressure-overload failing RV with persistent pulmonary vascular disease, which may improve quality of life and/or survival of PAH patients.