Until recently it was thought that human heart (like other mammals’ heart) is a terminally differentiated postmitotic organ. It was believed that shortly after birth cardiomyocytes lose their ability to proliferate and from this moment their amount is constant and further growth is by increasing the size of existing cells (hypertrophy). The following observations resulted in changing this dogma:

1. Between birth and early youth cardiomyocytes number increases (hyperplasia). In newborns both heart ventricles are built from ~1 x 10⁹ cardiomyocytes while in 20-year-olds their amount is several times larger – in males there are ~5.8 x 10⁹ cardiomyocytes in the right ventricle and 2.0 x 10⁹ cardiomyocytes in the left ventricle, in women there are ~4.5 x 10⁹ and 1.4 x 10⁹ respectively (1).

2. Apart from apoptosis (2) and necrosis (3) in myocardium, the total number of cardiomyocytes in an adult heart is on a relatively constant level. It means that dying cardiomyocytes are replaced by new cells which are created from specific cardiac stem cells (2). Estimated calculations based on the ¹⁴C concentration measurements in myocardium of people exposed to increased ¹⁴C concentration in the air in the youth (as a result of nuclear tests in the cold war period) suggest that cardiomyocytes are renewed with gradual decrease from ~1% turning over annually at age 20 to ~0.45% at the age 75. It means that during a norma lifespan about 50% cardiomyocytes would be exchanged (4). Newer analyses taking the frequency of apoptosis in myocardium into consideration show that the turnover of cardiomyocytes in human heart is much faster and this process even accelerates with age (5). According to these estimates in male heart cardiomyocytes replacement occurs at a rate 7, 12 and 32% per year at 20, 60 and 100 years of age. In women this process is even more intense and corresponding values are 10, 14 and 40% per year, respectively. It means that cardiomyocytes are renewed 11-15 times between 20 and 100 years of age. The rest of myocardial cells such as fibroblasts and endothelial cells are also dynamically restored (6).

3. The chimerism phenomenon. In males who had female heart transplanted after some time there are cardiomyocytes, endothelial cells and smooth muscle cells with male Y chromosome in myocardium (7). The similar phenomenon is observed in women being recipients of male bone marrow, with time in their myocardium there are cells with chromosome Y (8). These results suggest recruitment of peripheral stem cells to the heart (e.g. from the bone marrow) and creating myocardial cells de novo.

4. Cardiac stem cells (CSC) are the cells reside in the myocardium that can differentiate into cardiomyocytes, smooth muscle cells, endothelial cells and fibroblasts. At present there is not any good marker allowing to identify them and CSC include several subpopulations: (a) cell expressing receptor c-kit, (b) cell expressing stem cell antigen 1 (Sca 1), (c) cell expressing transcription factor Isl 1, (d) cells abilities to efflux the Hoechst 33342 dye so called side-population (SP) cells and (e) cardiosphere-derived cells (9-11). In the heart CSC are stored in a special structure called niches located in the apex and atria. CSC are sensitive to substances released from damaged cardiomyocytes, inter alia hepatocyte growth factor (HGF) and vessel endothelium growth factor (VEGF). These factors promote CSC proliferation and their migration from niches to damaged myocardial areas (12). According to the theory that in tissues there are heterogeneous populations of stem cells directed to different tissues and organs, CSC may also be found in bone marrow and peripheral organs.

Research of the past years show that cardiomyocytes lost in physiological apoptosis and/or necrosis are replacement by new cells formed by asymmetric mitotic divisions of cardiac stem cells. In pathological conditions there may be disturbances in the natural processes of heart regeneration. This may be a result of increase in apoptosis/necrosis of myocardial cells or impairment of regeneration abilities of cardiac stem cells. As a result it may lead to net loss of constrictive cells with the following remodeling, hemodynamic decompensation and heart failure. For years there has been intensive research on the possibility of increasing regenerative potential of the heart and using it in treatment for acute myocardial infarction and post--ischemic heart failure.

At present there are two treatment strategies of increasing regenerative potential of the heart. The first is to increase the regenerative ability of myocardium by mobilization of endogenous bone marrow derived and cardiac stem cells. Experimental studies in this field showed that application of SCF (stem cell factor) and G-CSF (granulocyte colony stimulating factor) to mice with myocardial infarction leads to mobilization of bone marrow stem cells. After 27 days the infarcted area was occupied by 15 x 10⁶ new cardiomyocytes, which resulted in 40% reduction of the infarct size. There were also new microvessels and hemodynamic parameters improved (13). However, the results of the clinical research on the influence of pharmacological stem cell mobilization from bone marrow by G-CSF in patients with acute myocardial infarction are unclear (14).

The second strategy is to increase the number of progenitor cells in the myocardium by application of different types of exogenous stem cells, which could potentially repair damaged myocardium. The direction of this research was determined by pioneer works of the Anversa’s group (15), which showed that the subpopulation of mononuclear marrowy stem cells injected directly in the damaged mouse heart is able to regeneration it. After 9 days from cells application about 68% of the infracted area was occupied by newly formed cardiomyocytes, there were new and there was improvement in hemodynamic parameters of the left ventricle. Using exogenous stem cells, their different subpopulations, in regenerative heart therapy is at present the most dynamic field of research.