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

Authors:
Eric G Schmuck
Eric G Schmuck
University of Wisconsin
United States
Timothy A Hacker
Timothy A Hacker
University of Wisconsin-Madison
United States
David A Schreier
David A Schreier
University of Wisconsin-Madison Madison
United States
Naomi C Chesler
Naomi C Chesler
University of Wisconsin-Madison
United States
Zhijie Wang
Zhijie Wang
University of Wisconsin-Madison
United States

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

Department of Biomedical Engineering, University of Wisconsin , Madison, Wisconsin.

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.

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http://dx.doi.org/10.1152/ajpheart.00091.2018DOI Listing
May 2019
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References

(Supplied by CrossRef)
Article in Q J Nucl Med Mol Imaging
Caveliers V et al.
Q J Nucl Med Mol Imaging 2007

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