![]() To vary the dosage of the applied cardiomyocyte number, we generated EHTs with different cell densities (cell-free, fibrin patches without cells dose 1, 9×10 6 cells dose 2, 12×10 6 cells and dose 3, 15×10 6 cells per 1.5 mL). Care was taken to suture the patch onto the healthy myocardium adjacent to the scar. Patch EHTs were sutured above the scar 7 days after injury. 9 Cryo-injury of the left ventricular wall was induced in female guinea pigs (300–450 g, 8–9 weeks of age, Charles River and Envigo). Myocardial injury was induced as previously described. Injury Model and EHT Patch Transplantation The present study describes the generation of EHT patches under GMP-compatible conditions that can be scaled to a clinically relevant size, evaluated the effect of EHT-patch transplantation in a dose-finding study in guinea pigs, and assessed the possibility to transplant human-scale EHT patches in pigs. In addition, the optimal dose has not yet been defined. Upscaling from small-animal models to humans and adaptation to good manufacturing practices (GMPs) represent challenges. 9 Yet, hurdles toward clinical translation remain. 8–11 We have recently shown that transplantation of 2 strip-format human engineered heart tissues (EHTs) improved left ventricular function in a guinea pig model. 6, 7 Pluripotent stem cell–derived cardiomyocytes have repeatedly demonstrated their potential to regenerate injured hearts in preclinical models. Regenerative strategies that aim to generate new myocardium are currently being evaluated in preclinical 5 and first clinical trials. 3 Cardiomyocyte renewal is limited to ≈1% per year, and, even though there is evidence that cardiomyocyte proliferation increases slightly after injury, this is by far too little to form a physiologically relevant number of new cardiomyocytes. 1 Although mortality from acute myocardial infarction has decreased substantially over the past 2 decades, 2 heart failure as its main sequela remains a major disease burden. Heart disease is the number one cause of death worldwide. Customer Service and Ordering Information.Stroke: Vascular and Interventional Neurology. ![]() ![]() Journal of the American Heart Association (JAHA).Circ: Cardiovascular Quality & Outcomes.Arteriosclerosis, Thrombosis, and Vascular Biology (ATVB).
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