Abstract 13867: A Tissue Engineered Chondrocyte Cell-Sheet Induces Extracellular Matrix Modification to Enhance Ventricular Biomechanics and Attenuate Myocardial Stiffness in Ischemic Cardiomyopathy
Introduction: There exists a substantial body of work describing cardiac support devices to mechanically support the left ventricle (LV); however, these devices lack biological effects. To remedy this, we implemented a cell-sheet engineering approach utilizing chondrocytes, which in their natural environment produce a relatively elastic extracellular matrix (ECM) for a cushioning effect. Therefore, we hypothesized that a chondrocyte cell-sheet applied to infarcted and borderzone myocardium will biologically enhance the ventricular ECM and increase elasticity to augment cardiac function in a model of ischemic cardiomyopathy (ICM).
Methods and Results: Primary articular cartilage chondrocytes of Wistar rats were isolated and cultured on temperature-responsive culture dishes to generate cell-sheets. A rodent ICM model was created by ligating the left anterior descending coronary artery. Rats were divided into two groups: cell-sheet transplantation and no treatment. The cell-sheet was placed onto the surface of the heart covering the infarct and borderzone areas. At 4 weeks following treatment, the decreased fibrotic extension and increased elastic microfiber networks in the infarct and borderzone areas correlate with this technology’s potential to stimulate ECM formation. The enhanced ventricular elasticity was further confirmed by the axial stretch test, which revealed that the cell-sheet significantly attenuated tensile modulus, a parameter of stiffness. This translated to increased wall thickness in the infarct area, decreased LV volume, and the improvement of LV function as indicated by echocardiography and pressure-volume analyses. (Table)
Conclusions: The chondrocyte cell-sheet strengthens the ventricular biomechanical properties by inducing the formation of elastic microfiber networks in ICM, resulting in attenuated myocardial stiffness and improved myocardial function.
- © 2013 by American Heart Association, Inc.