Cardiac Repair From Within and Outside

Heart failure often develops as a consequence of the limited endogenous capacity for cardiac regeneration after acute myocardial infarction (MI). Cardiac progenitor cells (CPCs) that have been transplanted into hearts with MI can repair the damaged myocardium to some degree despite their low engraftment rates and limited evidence of transdifferentiation into myocardial cells. However, as progenitor-based and stem cell–based tissue engineering technologies continue to evolve, it now seems possible to deposit and retain large numbers of therapeutic cells in close proximity to the region of myocardial tissue damage, and even to replace scar tissue, thus preventing scar bulging and LV dilation, reducing wall stress at the border zone (BZ) of the infarct, improving myocardial bioenergetics, and, finally, remuscularizing the heart. Tissue-engineered cardiomyoplasty, using engineered myocardium or cell sheets, was first introduced at the beginning of the millennium. Recently, the paracrine activity of the engineered tissue has been enhanced by using fibrin patches as the cell carrier. Importantly, evidence of myocardial salvage has been obtained with both the direct remuscularization and paracrine approaches in rodent and porcine allograft models. Paracrine factors led to significant increases in BZ vascular density and in the regeneration of myocytes from endogenous CPCs. Although these reports suggest that tissue-engineered patches could have therapeutic potential for the repair of myocardial injury, the overall engraftment rate and biophysical integration of grafts need further optimization. Engineering cardiac patches for heart repair is a challenging biotechnological objective. This review summarizes the progress in cardiac patch engineering (Table) and critically analyzes the problems and considerations that have to be incorporated into the design of an optimal engineered cardiac patch for heart failure therapy. Despite the relatively straightforward biological rationale, the mechanisms responsible for the observed therapeutic effects are, in most cases, Review