Generation of a Human Cardiac Patch Based on a Reendothelialized Biological Scaffold (BioVaSc)

Although there are improvements in acute care, ischemic heart disease is the major cause of death worldwide. As a treatment for heart failure or heart infarction, stem cell therapies emerged as a potential therapeutic option. First results have shown moderate improvements and have revealed several limitations, such as an insufficient retention, homing, and engraftment of the cells. These drawbacks result in a loss of cells shortly after implantation. To overcome these hurdles, a human cardiac patch is developed in this work, using a biological collagen‐based vascularized scaffold (BioVaSc®). Endothelial cells are cultured in the pre‐existing vascular structure to establish a physiological blood‐tissue interface. A co‐culture of fibroblasts, mesenchymal stem cells, and induced‐pluripotent‐stem‐cell‐derived cardiomyocytes is seeded on the vascularized scaffold. After two weeks, physiological cardiac functions and expression of cardiac‐specific markers is detected. Moreover, physiological beating rates as well as responsiveness to drug treatment and electrical stimulation is observed. Bioreactor culture facilitates long‐term culture up to four months. Due to its tissue characteristics, the patch constitutes a promising tool for drug development, in addition to its potential in clinical applications. A biological vascularized scaffold (BioVaSc) is used to generate a functional cardiac patch. Human induced‐pluripotent‐stem‐cells‐derived cardiomyocytes are seeded in coculture with human dermal fiboblasts and human mesenchymal stem cells onto the BioVaSc following repopulating the vasculature with human endothelial cells. Dynamic bioreactor culture enables long‐term stable (four months) functional cardiac patches with physiological characteristics.