Dynamics of Cell Generation and Turnover in the Human Heart

• Published in: Cell Vol. 161; no. 7; pp. 1566 - 1575
• Main Authors: Bergmann, Olaf, Zdunek, Sofia, Felker, Anastasia, Salehpour, Mehran, Alkass, Kanar, Bernard, Samuel, Sjostrom, Staffan L., Szewczykowska, Mirosława, Jackowska, Teresa, dos Remedios, Cris, Malm, Torsten, Andrä, Michaela, Jashari, Ramadan, Nyengaard, Jens R., Possnert, Göran, Jovinge, Stefan, Druid, Henrik, Frisén, Jonas
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 18.06.2015; Elsevier
• Subjects: Basic Medicine; Cell and Molecular Biology; Cell- och molekylärbiologi; Dynamical Systems; Endothelial Cells - cytology; Heart - physiology; Humans; Leukocyte Common Antigens - metabolism; Mathematics; Medical and Health Sciences; Medicin och hälsovetenskap; Medicinska och farmaceutiska grundvetenskaper; Mesoderm - cytology; Myocardium - cytology; Myocytes, Cardiac - cytology; Polyploidy; Radiometric Dating
• ISSN: 0092-8674; 1097-4172; 1097-4172
• DOI: 10.1016/j.cell.2015.05.026

The contribution of cell generation to physiological heart growth and maintenance in humans has been difficult to establish and has remained controversial. We report that the full complement of cardiomyocytes is established perinataly and remains stable over the human lifespan, whereas the numbers of both endothelial and mesenchymal cells increase substantially from birth to early adulthood. Analysis of the integration of nuclear bomb test-derived 14C revealed a high turnover rate of endothelial cells throughout life (>15% per year) and more limited renewal of mesenchymal cells (<4% per year in adulthood). Cardiomyocyte exchange is highest in early childhood and decreases gradually throughout life to <1% per year in adulthood, with similar turnover rates in the major subdivisions of the myocardium. We provide an integrated model of cell generation and turnover in the human heart. [Display omitted] [Display omitted] •The number of cardiomyocytes remains constant during the human lifespan•Endothelial and mesenchymal cells increase into adulthood and show high turnover•Cardiomyocyte turnover decreases exponentially with age and is <1% per year in adults•The cardiomyocyte turnover rate is equal in the main subdivisions of the human heart A comprehensive analysis of cell generation and turnover in the human heart demonstrates that cardiomyocyte numbers are constant throughout the human lifespan, with a low turnover rate. Endothelial and mesenchymal cells are exchanged at a high rate, and their numbers increase into adulthood.