This suggests that children and adolescents may be able to regenerate myocardium, that abnormal cardiomyocyte proliferation may be involved in myocardial diseases that affect this population, and that these diseases might be treatable through stimulation of cardiomyocyte proliferation.–4).
The only currently available, definitive therapy—heart transplantation—is limited by donor availability.
In the present study, we examined a set of 21 healthy young (age range from 0–20 y) hearts and an additional set of 15 adult hearts (, Table S1).
Our aim was to determine the extent and timing of cardiomyocyte cell cycling, proliferation, and hypertrophy and to relate the activity of these mechanisms to the growth of the human heart.). Scale bar: 50 μm (To be able to use flash-frozen human myocardial samples, we developed a unique isolation method, which involves fixing the myocardium before digestion with collagenase.
The detection of thymidine analogs, used to quantify cardiomyocyte turnover in adult cancer patients (18), is also not feasible in children.
Thus, due to multiple limitations, little is known about the cellular growth mechanisms in the human heart in the most dynamic time window between birth and 20 y of age.
The human heart is believed to grow by enlargement but not proliferation of cardiomyocytes (heart muscle cells) during postnatal development.
To overcome these limitations, we have developed and implemented image-based assays.Confocal microscopy and visual quantification showed agreement between these markers in the identification of cardiomyocyte nuclei () on three random myocardial sections from different sites of the same left ventricle (LV) showed no significant differences in the nuclear density in different compartments of the same LV, indicating that our sampling method yielded a probe representative of the whole LV.We determined fixation-related tissue shrinkage to be 21 ± 5.8% and corrected the results accordingly ().In biological models that, unlike adult humans, regenerate myocardium, cardiomyocyte proliferation is important for regeneration as well as postnatal heart growth (10, 11).For example, in mice, developmental cardiomyocyte proliferation continues for up to day 7 after birth, which coincides with the loss of regenerative capacity (11, 12).