Career:Engineered Diseased Myocardial Model For Cell-Based Therapy

Cardiovascular disease including myocardial infarction (MI) is the leading cause of death in the Western world. Over the past decade, numerous preclinical studies and clinical trials using cell-based therapies have been performed to rEnvironmental Protection Agencyir or regenerate a damaged heart. One of the major hurdles in cell-based therapy is a lack of mechanistic understanding of observed therapeutic effects. To understand the functional benefits of transplanted cells, it is imperative to study the biological activity of transplanted cells in the diseased myocardial environment. Existing models however, focus almost exclusively on mimicking the healthy cardiac microenvironment with the goal of providing a living surgical replacement. This CAREER proposal takes a principal tissue engineering approach to develop a novel diseased model in vitro in order to study multi-phase myocardial healing and rEnvironmental Protection Agencyir. This model with independent control of cell and extracellular components will serve as a powerful tool to investigate the mechanisms of cardiovascular disease and rEnvironmental Protection Agencyir providing a major step toward making cell-based therapies more effective for patients with heart disease. Development and wide distribution of interactive educational and training tools developed in the course of the proposed research will facilitate fundamental advances in basic STEM areas as well as in the practical application of cardiovascular tissue engineering for regenerative medicine and clinical settings. The objective of the proposed CAREER research is to advance understanding of the underlying mechanisms of rEnvironmental Protection Agencyir by cell-based therapy in injured myocardium. The proposal aims to develop an in vitro diseased myocardial tissue model recapitulating disease progression following myocardial damage. The proposed engineered disease model will function as a ventricular pump replicating key characteristics of natural or infarcted myocardium. The specific goals are to: (1) Engineer a well-controlled diseased myocardial model mimicking the first two stages of the rEnvironmental Protection Agencyrative process post-MI, which is the time when most cell-based therapies are performed. (2) Determine the interaction between host cells and transplanted stem cells and (3) Investigate the mechanism of the host extracellular matrix and grafted cell interaction to understand the specific role of the local infarct environment on transplanted cell function during post-MI healing process. The results from this study will address two unknown areas that currently limit the success of cell-based therapies for cardiac regeneration. The two unknowns are (1) underlying fundamental mechanisms that drive functional integration of the transplanted cells and (2) optimal timing of the therapy. Such insights will facilitate the translation of tissue engineering solutions from the lab to patients by enhancing the practical efficacy of cell-based therapy in clinics.