Beneficial effects of mesenchymal stem cell delivery via a novel cardiac bioscaffold on right ventricles of pulmonary arterial hypertensive rats.
Animals
Arterial Pressure
Cells, Cultured
Disease Models, Animal
Fibrosis
Hypertrophy, Right Ventricular
/ etiology
Hypoxia
/ complications
Indoles
Male
Mesenchymal Stem Cell Transplantation
/ methods
Myocardial Contraction
Myocardium
/ metabolism
Pulmonary Arterial Hypertension
/ etiology
Pulmonary Artery
/ physiopathology
Pyrroles
Rats, Sprague-Dawley
Recovery of Function
Regeneration
Tissue Scaffolds
Ventricular Dysfunction, Right
/ etiology
Ventricular Function, Right
Ventricular Remodeling
von Willebrand Factor
/ metabolism
cardiac patch
paracrine effect
pulmonary hypertension
regenerative medicine
right heart
Journal
American journal of physiology. Heart and circulatory physiology
ISSN: 1522-1539
Titre abrégé: Am J Physiol Heart Circ Physiol
Pays: United States
ID NLM: 100901228
Informations de publication
Date de publication:
01 05 2019
01 05 2019
Historique:
pubmed:
2
3
2019
medline:
17
3
2020
entrez:
2
3
2019
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 30822119
doi: 10.1152/ajpheart.00091.2018
pmc: PMC6580387
doi:
Substances chimiques
Indoles
0
Pyrroles
0
von Willebrand Factor
0
Semaxinib
71IA9S35AJ
Types de publication
Comparative Study
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
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