Vascular Perfusion of Implanted Human Engineered Cardiac Tissue

Regeneration of muscle tissue in the heart after a myocardial infarction requires delivering human cardiomyocytes that will survive and integrate with the host myocardium. Of primary importance is the development of a vascular bed to nourish the implanted cardiomyocytes, whether delivered via injection or in engineered tissues. Co-culture of hESC-derived cardiomyocytes, human endothelial cells, and human stromal cells provides a prevascular network in scaffold-free engineered tissue patches. As a result, the density of lumen structures in the graft increases by histological analysis, but perfusion of these vessels must be assessed. In this study, we develop a method for perfusing the host heart and engineered human cardiac tissue graft that is compatible with confocal microscopy for obtaining 2D images and 3D reconstructions of the graft vasculature. We demonstrate that, although vascular density is substantial in the grafts, flow remains sluggish. Further improvements in arterial remodeling or vascular engineering are required for physiological levels of blood flow.