During a myocardial infarction, or heart attack, cardiac tissue is deprived of oxygenated blood, which causes cardiomyocytes, the muscle cells of the heart, to die. This death of tissue impairs the heart's ability to function efficiently, and adult cardiomyocytes renew themselves at a low rate that effectively precludes regeneration of mature cardiac muscle. For this reason researchers studying cardiovascular disease are particularly interested in determining the age and conditions within which cardiomyocytes do proliferate. In humans it has been shown that most cardiomyocytes are generated during early childhood, but it was not known if or how this pattern of growth applies to other models of cardiovascular disease, including the mouse.

To address this question, Olaf Bergmann of Karolinska Institutet (Solna, Sweden) and colleagues isolated and examined hearts from mice, collected at different points during the first three weeks after birth. Bergmann's team used stereology, flow cytometry and immunohistochemistry in a variety of applications to determine cardiomyocyte counts, DNA synthesis and cell cycle activity change during early postnatal development in mice (Cell 163, 1026–1036; 2015).

From these different approaches the researchers came to the conclusion that “in the uninjured neonatal mouse heart, up to 30% of all cardiomyocytes are generated even after postnatal day 2, and the full complement of cardiomyocytes (>95%) is reached after 11 days.” This pattern of growth and development is similar to that seen in humans, with some minor differences. For instance, following early cell proliferation and DNA synthesis, approximately 60% of cardiomyocyte nuclei are polyploid in mature humans, whereas only 10% of cardiomyocyte nuclei are polyploid in mature mice. However, the authors note, the process by which cardiomyocytes become polyploid takes place at a similar stage in both species (during preadolescence). The researchers noted that in mice, this polyploidization occurs mainly during the second and third weeks after birth.

With these findings, Bergmann's team has improved upon the use of mice to study cardiovascular growth and regeneration, confirming essential similarities and distinguishing important differences between the murine cardiovascular model and the human heart. In doing so, they have also advanced research toward understanding the regenerative capabilities of the murine and human hearts. “The next step is to understand why most heart muscle cells stop dividing so early in life,” Olaf Bergmann asserted in a press release. “Our aim is to help the adult heart to generate new muscle cells to replace lost heart tissue after injuries.”