Mitral Valve Prolapse: A Tissue Engineering Model
Collin Owens, Agneta Simionescu.
Clemson University, Clemson, SC, USA.
OBJECTIVE: The purpose of this study was to develop an in vitro model for mitral valve (MV) prolapse. This pathology is mainly due to myxomatous degeneration, a process associated with altered mechanical stress and turbulent flow. The prolapsed valve presents enlarged and thickened "floppy" leaflets, associated with chordal elongation, thinning, and/or rupture, and severe annular dilation.
METHODS: Based on tissue engineering principles, we developed a non-immunogenic scaffold, using the porcine mitral valve as starting material, and remove the porcine cells without damaging the matrix components. The scaffold was seeded with valvular interstitial cells (VICs) and valvular endothelial cells (VECs) and placed in a custom MV bioreactor, able to simulate physiological and pathological conditions. After 1 week, the valves were analyzed for cell viability, cell activation, mechanical properties, and matrix integrity, using histology and immunohistochemistry techniques.
RESULTS: VICs and VECs seeded interstitially and on the surface of leaflet scaffolds became activated under diabetic and high-pressure conditions. Changes in extracellular composition, structure and mechanical properties further support that cellular activation and matrix remodeling were occurring. Indeed, by controlling and varying the mechanical conditions and biochemical composition of the valve environment, we could create a 3D model of living MV for studying cell and matrix alterations, as well as the cell-cell and cell-matrix interactions that lead to dysfunctional remodeling in MV disease.
CONCLUSIONS: It was shown that tissue engineered mitral valves conditioned in our bioreactor could serve as a model for mitral valve prolapse. Our studies could lead towards an understanding of how the valve microstructural alterations represent an early effort to compensate for altered physiologic loading to reduce stress and maintain coaptation. Furthermore, this method could serve as a base for studies of pharmacological treatments of the mitral valve apparatus.
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