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Friday April 20, 2018 -- Engineered Cells and Tissues for Treatment of Ischemic Heart Disease and Arrhythmias

SMBB 2650, 11:45 am

Speaker: Nenad Bursac , Professor of Biomedical Engineering, Medicine, and Cell Biology , Duke University

Presentation Abstract:

In this talk, I will present our recent progress on the development of engineered cells and tissues for cardiac therapy. I will first describe a scalable methodology for engineering functional human heart tissues resulting in the first-time generation of a large, highly functional human cardiac tissue patch with clinically relevant dimensions. These studies have shown that specific combinations of biomaterials, dynamic culture environment, and supporting non-myogenic cells can rapidly advance structural and electromechanical maturation of engineered myocardium in vitro to a level approaching that of the native adult heart tissue. I will further describe our efforts to incorporate pluripotent stem cell derived vascular networks within human heart tissue patches to facilitate patch perfusion and survival in vivo. In the second part of my talk, I will describe our research on converting human unexcitable fibroblasts into an autonomous source of electrically excitable and actively conducting biosynthetic cells. Specifically, I will show that forced expression of a minimum of three ion channels is sufficient to achieve this goal, and that mutagenesis of the expressed channels can serve to specifically tailor electrical properties of the generated cells. These genetically engineered cells can electrically bridge separated cardiomyocytes and augment action potential conduction and contractile function. I will further show that the viral delivery of engineered prokaryotic sodium channels to a fibrotic cardiac substrate can induce gain-of-excitability effects to both improve impulse conduction and reduce incidence of reentrant arrhythmias. Together, these results open doors to new studies of human excitable tissue function, disease, and regeneration, and lay foundation for the development of novel therapies for heart disease.