Beneficial effects of mesenchymal stem cell delivery via a novel cardiac bioscaffold on right ventricles of pulmonary arterial hypertensive rats

Am J Physiol Heart Circ Physiol. 2019 May 1;316(5):H1005-H1013. doi: 10.1152/ajpheart.00091.2018. Epub 2019 Mar 1.


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 right ventricle (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 with 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 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. NEW & NOTEWORTHY We explored the effects of mesenchymal stem cell-seeded bioscaffold on right ventricles (RVs) of rats with established pulmonary arterial hypertension (PAH). Some beneficial effects were observed despite persistent PAH, suggesting that this may be a new therapy for RV to improve quality of life and/or survival of PAH patients.

Keywords: cardiac patch; paracrine effect; pulmonary hypertension; regenerative medicine; right heart.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Arterial Pressure*
  • Cells, Cultured
  • Disease Models, Animal
  • Fibrosis
  • Hypertrophy, Right Ventricular / etiology
  • Hypertrophy, Right Ventricular / metabolism
  • Hypertrophy, Right Ventricular / physiopathology
  • Hypertrophy, Right Ventricular / surgery*
  • Hypoxia / complications
  • Indoles
  • Male
  • Mesenchymal Stem Cell Transplantation / methods*
  • Myocardial Contraction
  • Myocardium / metabolism
  • Myocardium / pathology
  • Pulmonary Arterial Hypertension / etiology
  • Pulmonary Arterial Hypertension / metabolism
  • Pulmonary Arterial Hypertension / physiopathology
  • Pulmonary Arterial Hypertension / surgery*
  • Pulmonary Artery / physiopathology*
  • Pyrroles
  • Rats, Sprague-Dawley
  • Recovery of Function
  • Regeneration
  • Tissue Scaffolds*
  • Ventricular Dysfunction, Right / etiology
  • Ventricular Dysfunction, Right / metabolism
  • Ventricular Dysfunction, Right / physiopathology
  • Ventricular Dysfunction, Right / surgery*
  • Ventricular Function, Right*
  • Ventricular Remodeling
  • von Willebrand Factor / metabolism


  • Indoles
  • Pyrroles
  • von Willebrand Factor
  • Semaxinib