Putting the Heart Back Together: Engineering Cardiac Regeneration from the Molecular to Tissue Scales

11/06/2009 - 5:00pm to 6:00pm
Adam W. Feinberg, Ph.D. - Disease Biophysics Group, School of Engineering and Applied Sciences, Harvard University
Biomedical Sciences Building JG32

The diseased and damaged heart has limited regenerative capacity, leading to cardiac failure being the number one cause of death in the United States.  Myocardial regeneration is one therapeutic solution but it faces two major challenges; (i) obtaining differentiated cardiomyocytes in sufficient number and (ii) organizing these cardiomyocytes into a functional tissue.  Specifically, cardiac muscle needs electromechanical coupling and structure-function relationships to be properly organized from the actin-myosin motors and ion channels up to the whole heart.  I will describe recent developments in cardiac tissue engineering that have enabled us to regenerate the multiscale, hierarchical coupling of native muscle tissue in vitro in order to elucidate how structural variations underlie physiologic and pathologic function.  Rather than recapitulating the whole heart, or even an entire ventricle, I will focus on the contractility of 2-dimensional myocardial sheets that mimic the lamellar layers of the ventricular wall.  These muscular thin films (MTFs) are engineered with specific contractile properties by controlling the microcontact printing parameters of extracellular matrix proteins used to direct 2D myogenesis.  Results will show that this microscale control of cell structure and cell-cell coupling dictates gene expression, ion channel function and tissue-scale contractility.  This enables the creation of in vitro disease states that recapitulate various in vivo cardiomyopathies.  I will explain how to leverage this system for high-content drug discovery/screening and as a platform for developing stem cell based regenerative cardiac therapies.

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