Design of an electrical stimulation platform for the in vitro maturation of human adult cardiomyocytes

According to the World Health Organization, cardiovascular diseases are the major cause of death worldwide, representing 32% of all global death, 85% of which are due to heart attack and stroke. During myocardial infarction a large number of cells die within the area subjected to ischemia, in the first 6 to 24 hours. However, heart has a very limited self-regeneration capacity leading to a permanent loss of cardiomyocytes in the site of the ischemic event. Moreover, fibroblasts change their phenotype into myofibroblasts, leading to increased collagen deposition, tissue stiffening and consequent heart failure. Conventional pharmaceutical therapies target mechanisms against maladaptive regulators activated by left ventricular dysfunction, such as inhibitors of the renin-angiotensin system, the mineralocorticoid receptor, the sympathetic nervous system and, more recently, the natriuretic system. These drugs reduce mortality, but they fail to resolve the loss of cardiomyocytes and blood vessels, and are not curative. Cardiac regenerative medicine aims to regenerate cardiac tissue by repopulating the injured heart with new functional cardiomyocytes. In vivo animal models are the current gold standard to preclinically test new therapies to achieve this aim, but they are unable to recapitulate human physiology, leading to failures during clinical trials. In vitro models of diseased human cardiac tissues woud represent promising alternative testing platforms to screen new therapeutic approaches. In this work, a in vitro model of 3D cardiac tissue, based on the application of an electrical stimulation to 3D cultured human cardiac cells, was developed and characterized, showing superior cell maturation to unstimulated 3D cultures and traditional 2D cultures.