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OF THE DISSERTATION REGULATION OF BONE MARROW STEM CELLS THROUGH OSCILLATORY SHEAR STRESSES A HEART VALVE TISSUE ENGINEERING PERSPECTIVE by Sasmita Rath Florida International University, 2015 Miami, Florida Professor Sharan Ramaswamy, Major Professor Heart valve disease occurs in adults as well as in pediatric population due to age-related changes, rheumatic fever, infection or congenital condition. Current treatment options are limited to mechanical heart valve (MHV) or bio-prosthetic heart valve (BHV) replacements. Lifelong anti-coagulant medication in case of MHV and calcification, durability in case of BHV are major setbacks for both treatments. Lack of somatic growth of these implants require multiple surgical interventions in case of pediatric patients. Advent of stem cell research and regenerative therapy propose an alternative and potential tissue engineered heart valves (TEHV) treatment approach to treat this life threatening condition. TEHV has the potential to promote tissue growth by replacing and regenerating a functional native valve. Hemodynamics plays a crucial role in heart valve tissue formation and sustained performance. The focus of this study is to understand the role of physiological shear stress and flexure effects on de novo HV tissue formation as well as resulting gene and protein expression. A bioreactor system was used to generate physiological shear stress and cyclic flexure. Human bone marrow mesenchymal stem cell derived tissue constructs were exposed to native valve-like physiological conditioning. Responses of these tissue constructs to the valve-relevant stress states along

Regulation of Bone Marrow Stem Cells through Oscillatory Shear Stresses - A Heart Valve Tissue Engineering Perspective