Tissue engineered heart repair from preclinical models to first-in-patient studies

The lack of regenerative therapies for the treatment of degenerative diseases, such as heart failure, motivates the search for cell therapeutics. From a technical point of view, cell-based heart repair is approached from two angles: (1) by injection of cells and (2) by epicardial implantation of tissue engineered constructs. The choice of cells depends on the therapeutic strategy and goal. Non-myocytes are primarily explored for their protective paracrine activity. Cardiomyocytes are implanted to remuscularize the heart by their electromechanical integration. Sufficiently long retention of cell implants is a key challenge for any cell therapy. Ample evidence exists for enhanced and sustainable cell retention if applied via tissue engineering approaches. The introduction of human pluripotent stem cells is a door opener for clinical translation. How to best study and estimate therapeutic efficacy of human cells, in particular stem cell-derived cardiomyocytes, in preclinical models remains a matter of debate. This review discusses key features of engineered myocardium designed for clinical use and reviews models for the preclinical evaluation of tissue engineered heart repair.