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Jun 27, 2013
 |  BC Innovations  |  Tools & Techniques

Finding drugs for the faint of heart

Harvard University researchers have developed an organ on a chip that recapitulates genetic, morphological and functional markers of failing myocardium.1 The system could help identify therapeutic candidates that slow or reverse heart failure with better reliability than current in vitro culture systems.

Traditional in vitro models of heart failure involve exposing cultured cardiomyocytes to chemical or mechanical stimuli that induce pathological gene expression, hypertrophy and remodeling.2-4

A Harvard team led by Kevin Kit Parker has been developing heart-on-a-chip systems that also recapitulate contractile function, which is considered a better proxy of cardiac output than changes in gene expression and electrophysiological properties. Parker is a professor of bioengineering and applied physics at Harvard and core member of the Wyss Institute for Biologically Inspired Engineering at Harvard University.

Parker's team previously used neonatal rat ventricular myocytes and its own muscular, thin-film technology to engineer an organ-on-a-chip microsystem that recapitulates the healthy myocardium.5 The system could be used to screen compounds for cardiotoxicity but not for the ability to correct a disease phenotype.

Now, the same group has engineered a microsystem that recapitulates the failing myocardium. The new chip consists of neonatal rat ventricular myocytes seeded on a fibronectin-patterned flexible silicone membrane. The chip further incorporates a custom-built multiwell system that allows the user to subject the engineered myocardium to uniaxial and cyclical stretch.

Cyclic stretching of myocardium recreated pathological heart failure-associated changes to myocyte shape, sarcomere alignment, calcium cycling and gene...

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