Stem cells and cardiomyocytes

Chronic heart diseases such as ischemia and hypertensive heart pathologies are characterized by irreversible loss of cardiomyocytes. Although terminally differentiated cardiomyocytes have been described as showing some evidence of mitotic division in the heart (Soonpaa and Field, 1994), the generally accepted paradigm in contemporary cardiology is that adult cardiomyocytes lack the ability to regenerate the myocardium because they proliferate only up to the time of birth. The concept has been questioned recently by two reports (Beltrami et al., 2003; Urbanek et al., 2003) describing a resident stem cell population in human and rodent hearts that proliferate and, at least in the case of the rat, are multipotent and able to give rise to cardiomyocytes, vascular smooth muscle cells, and endothelial cells. While the robustness of these findings still requires independent verification, cell transplantation for the treatment of cardiac disease remains an attractive concept and finding the most suitable source of cells for this purpose is one of the most exciting challenges of experimental cardiology at the present time. Stem cells are a much-discussed source of cells for transplantation, derived either from adult human tissues (adult stem cells) or from human embryos (embryonic stem cells). Both are considered as options deserving further research (reviewed in Passier and Mummery, 2003). However, in the light of ethical reservations about the use of human embryonic stem (ES) cells in many countries, it has been difficult in the ensuing debate to obtain a balanced viewof scientific developments. Here, we provide a brief introduction to adult and ES cells, describing the advantages and disadvantages of each with respect to transplantation, and provide the scientific background for understanding the current strategies being used to produce and identify the most suitable cells for restoring cardiac function. Understanding how cardiac cell fate is specified by extracellular cues and how the electrical phenotype of stem cellderived cardiomyocytes compares with that of the normal counterparts is essential if cell transplantation therapy is to become useful in restoring cardiac function.