Cardiovascular disease is an important cause of mortality in the Western world.
1 The central cellular mechanism underlying the development of myocardial dysfunction is a decrease in the number of viable cardiomyocytes as a result of ischaemic injury or ongoing apoptosis, and the inability of remaining cardiomyocytes to compensate the cell loss by cardiomyocyte regeneration. Stem cells have been studied intensively as a source of new cardiomyocytes to ameliorate injured myocardium and improve cardiac function.
2-4 The potential therapeutic benefit of stem cell transplantation has been investigated in animal models using bone marrow-derived cells,
5-8 cardiac stem cells,
5 embryonic stem (ES) cells
9,10 and foetal cardiomyocytes
11,12 by injecting them at the site of cardiac injury. The encouraging results reported in these animal studies led to the initiation of several clinical trials in which bone marrow derived cells and skeletal myoblasts were investigated.
4,13-16 However, the developmental plasticity of bone marrow cells to differentiate into cardiomyocytes has been questioned
17,18 and the predominant in vivo effect of bone marrow injection may be neoangiogenesis instead of muscle regeneration. Furthermore, autologous transplantation of skeletal myoblasts is confounded by the possible induction of life-threatening arrhythmias despite partial integration, survival and contribution to cardiac contractility.
15 Another source of transplantable cardiomyocytes is human embryonic stem cell (hES) derived cardiomyocytes. Although hES cells can be directed into the cardiomyocyte lineage, with a foetal phenotype,
19 their differentiation is not homogenous despite recent improvements in culture methods.
20,21 Furthermore, immunogenic, arrhythmogenic and especially ethical problems will limit their clinical use. These obstacles underscore the need to search for new sources of autologous adult cells to generate cardiomyocytes for regeneration of the failing myocardium. …
