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Recellularization of a novel off-the-shelf valve following xenogenic implantation into the right ventricular outflow tract. PLoS One 2017;12(8):e0181614 PMID: 28763463 PMCID: PMC5538661

Pubmed ID

28763463

DOI

10.1371/journal.pone.0181614

Abstract

Current research on valvular heart repair has focused on tissue-engineered heart valves (TEHV) because of its potential to grow similarly to native heart valves. Decellularized xenografts are a promising solution; however, host recellularization remains challenging. In this study, decellularized porcine aortic valves were implanted into the right ventricular outflow tract (RVOT) of sheep to investigate recellularization potential. Porcine aortic valves, decellularized with sodium dodecyl sulfate (SDS), were sterilized by supercritical carbon dioxide (scCO2) and implanted into the RVOT of five juvenile polypay sheep for 5 months (n = 5). During implantation, functionality of the valves was assessed by serial echocardiography, blood tests, and right heart pulmonary artery catheterization measurements. The explanted valves were characterized through gross examination, mechanical characterization, and immunohistochemical analysis including cell viability, phenotype, proliferation, and extracellular matrix generation. Gross examination of the valve cusps demonstrated the absence of thrombosis. Bacterial and fungal stains were negative for pathogenic microbes. Immunohistochemical analysis showed the presence of myofibroblast-like cell infiltration with formation of new collagen fibrils and the existence of an endothelial layer at the surface of the explant. Analysis of cell phenotype and morphology showed no lymphoplasmacytic infiltration. Tensile mechanical testing of valve cusps revealed an increase in stiffness while strength was maintained during implantation. The increased tensile stiffness confirms the recellularization of the cusps by collagen synthesizing cells. The current study demonstrated the feasibility of the trans-species implantation of a non-fixed decellularized porcine aortic valve into the RVOT of sheep. The implantation resulted in recellularization of the valve with sufficient hemodynamic function for the 5-month study. Thus, the study supports a potential role for use of a TEHV for the treatment of valve disease in humans.

Author List

Hennessy RS, Go JL, Hennessy RR, Tefft BJ, Jana S, Stoyles NJ, Al-Hijji MA, Thaden JJ, Pislaru SV, Simari RD, Stulak JM, Young MD, Lerman A

Author

Brandon J. Tefft PhD Assistant Professor in the Biomedical Engineering department at Medical College of Wisconsin




Scopus

2-s2.0-85026521104   5 Citations

MESH terms used to index this publication - Major topics in bold

Animals
Aortic Valve
Biomechanical Phenomena
Carbon Dioxide
Cell Proliferation
Cell Survival
Echocardiography
Extracellular Matrix
Female
Heart Valve Prosthesis
Heart Ventricles
Hemodynamics
Humans
Male
Phenotype
Prosthesis Design
Pulmonary Valve
Sheep
Swine
Tensile Strength
Tissue Engineering
Transplantation, Heterologous
jenkins-FCD Prod-353 9ccd8489072cb19f5b9f808bb23ed672c582f41e