Abstract 17349: The Biomimetic Cardiac Tissue Model (BCTM) Reproduces the Pathological Remodeling Seen in Hypertrophic and Dilated Cardiomyopathy

Abstract

Introduction: Cardiovascular research and regenerative strategies have been significantly limited by the lack of relevant cell culture systems that can recreate complex hemodynamic stresses associated with pressure-volume changes in the heart. To address this issue, we designed a Biomimetic Cardiac Tissue Model (BCTM) where encapsulated cardiac cells can be cultured in 3D fibers and subjected to hemodynamic loading to mimic pressure-volume changes seen in the left ventricle. Hypothesis: We tested the hypothesis that stimulation under hemodynamic loads as seen in pressure and volume overload is capable of reproducing the pathological remodeling seen in vivo. Methods: The 3D fibers are suspended between two posts within a pumping chamber that is integrated within a flow loop. Various parameters associated with heart function like heart rate, peak-systolic pressure, end-diastolic pressure and volume, end-systolic pressure and volume, and duration ratio between systolic and diastolic can all be precisely manipulated allowing culture of various cardiac cell types under developmental, normal, and disease states. Using the BCTM we reproduced the pathophysiological mechanical stresses of pressure overload and volume overload. Results: Using H9c2 cells, a cardiomyogenic cell line, our results clearly show that culture within the BCTM under pathological hemodynamic loads accurately induces morphological and gene expression changes similar to those seen in both hypertrophic and dilated cardiomyopathies in vivo . Cells within the BCTM under pressure overload see increased hypertrophic remodeling and fibrosis whereas cells subject to prolonged volume overload experience significant changes to cellular aspect ratio through thinning and elongation of the engineered tissue. Conclusions: These results clearly demonstrate that the BCTM can accurately reproduce pathological remodeling and create highly relevant models for cardiovascular disease modeling.