The ability of human pluripotent stem cells to differentiate towards the cardiac lineage has attracted significant interest, initially with a strong focus on regenerative medicine. The ultimate goal to repair the heart by cardiomyocyte replacement has, however, proven challenging. Human cardiac differentiation has been difficult to control, but methods are improving, and the process, to a certain extent, can be manipulated and directed. The stem cell-derived cardiomyocytes described to date exhibit rather immature functional and structural characteristics compared to adult cardiomyocytes. Thus, a future challenge will be to develop strategies to reach a higher degree of cardiomyocyte maturation in vitro, to isolate cardiomyocytes from the heterogeneous pool of differentiating cells, as well as to guide the differentiation into the desired subtype, that is, ventricular, atrial, and pacemaker cells. In this paper, we will discuss the strategies for the generation of cardiomyocytes from pluripotent stem cells and their characteristics, as well as highlight some applications for the cells. 1. Introduction Human cardiomyocytes can be isolated from heart biopsies, but the access to human heart tissue is very limited, and the procedure is complicated; it is difficult to obtain viable cell preparations in large quantities, and the cells obtained do not beat spontaneously. Thus, physiologically relevant in vitro models for human cardiomyocytes are currently limited. This has led in the creation of alternative models, such as isolation of cardiomyocytes from various newborn animals or production of genetically engineered cell lines overexpressing certain target proteins (e.g., ion channels) . All of these models, however, share significant limitations with respect to their basic physiological differences compared to human cardiomyocytes as well as high costs and ethical questions. A number of different human tissues have been proposed as the source of stem cells able to generate new cardiomyocytes (e.g., fetal cardiomyocytes, adult cardiac progenitor cells, skeletal myoblasts, bone marrow-derived stem cells, adipose-derived stem cells, umbilical cord-derived stem cells, and pluripotent stem cells) . The cardiac differentiation potential of adult, multipotent, stem cells found in fetal and adult tissues, however, is controversial [3, 4]. This has been attributed to the limited plasticity of adult stem cells, which precludes their differentiation into functional cardiomyocytes. The only adult stem cells that clearly have the potential to differentiate into
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