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Human cardiac muscle cells are the most physically energetic cells in the body, and according to various researchers they contain two nuclei in 25–40%. In humans, the heart during prenatal development consists mainly of cardiomyocytes with one nucleus. Just before birth, binucleation begins and can extend into early neonatal life. The physiological importance of binucleation is still poorly understood. In this critical review, we provide a summary of the latest research on binucleation of cardiac muscle cells, with special emphasis on the potential application of such knowledge to the fields of regenerative medicine. We summed up and discussed about ten possible biological arguments why binucleation may be beneficial for cardiac muscle cells as well as for the whole myocardium. These arguments include increase of gene expression, purposeful cell shaping, increase of metabolic activity, energy-saving growth and function, need for organ growth despite of telomere depletion, adaptation to stress (tissue regeneration), prevention of overgrowth – organ shaping, prevention of aneuploidy, terminally differentiated state (cardiomyocytes exit the cell cycle, end of proliferation activity); or, we hypothesize, binucleation is just an unwanted side product.

Two nuclei inside a single cardiac muscle cell. More questions than answers about the binucleation of cardiomyocytes