Mitral Valve Organ Culture Provides a Novel Experimental Paradigm
Grande-Allen, K. Jane
Doctor of Philosophy thesis
Mitral valve diseases and disorders affect tens of thousands of Americans each year, but understanding of the disease processes has yet to be fully developed. The behavior and characteristics of valve cells and tissue are highly dependent on their surrounding environment, including neighboring cells, extracellular matrix composition and 3D structure, mechanical forces, and signaling molecules both in the tissue and the circulation. In order to study native valve behavior and responses, an ex vivo bioreactor system was developed to culture whole mitral valves. The organ culture system simulated a physiologically relevant mechanical environment and provided nutrients and gas exchange. Valves cultured in this dynamic system retained more native cell and tissue characteristics than valves cultured in a static environment. To utilize this novel tool, a study was conducted to determine the effects of Angiotensin II on mitral valves, alone and in combination with the statin drug, Simvastatin.Angiotensin II was found to alter the native valve composition. Simvastatin inhibited some of these alterations, but accentuated others and also affected separate valve characteristics. In conclusion, an organ culture system for mitral valves has been designed, characterized, validated, and effectively put to use in a novel study.