Dynamics of Cell Generation and Turnover in the Human Heart
Olaf Bergmann
(1)
,
Sofia Zdunek
(1)
,
Anastasia Felker
(1)
,
Mehran Salehpour
(2)
,
Kanar Alkass
(3, 1)
,
Samuel Bernard
(4, 5, 6)
,
Staffan l. Sjostrom
(1)
,
Mirosława Szewczykowska
(7)
,
Teresa Jackowska
(8, 7)
,
Cris Dos remedios
(9)
,
Torsten Malm
(10)
,
Michaela Andrä
(11)
,
Ramadan Jashari
(12)
,
Jens r. Nyengaard
(13)
,
Göran Possnert
(2)
,
Stefan Jovinge
(14, 15, 16)
,
Henrik Druid
(3)
,
Jonas Frisén
(1)
1
Department of Cell and Molecular Biology [Stockholm]
2 Department of Physics and Astronomy [Uppsala]
3 Department of Forensic Medicine [Stockholm]
4 DRACULA - Multi-scale modelling of cell dynamics : application to hematopoiesis
5 ICJ - Institut Camille Jordan
6 MMCS - Modélisation mathématique, calcul scientifique
7 Szpital Bielański [Warsaw]
8 MCPE - Medical Center of Postgraduate Education [Warsaw]
9 Bosch Institute [Sydney]
10 Cardiothoracic Surgery [Lund]
11 Medical University of Graz = Medizinische Universität Graz
12 EHB - European Homograft Bank [Bruxelles]
13 Stereology and Electron Microscopy Laboratory [Aarhus]
14 Spectrum Health [Grand Rapids]
15 Van Andel Institute [Grand Rapids]
16 Lund Stem Cell Center
2 Department of Physics and Astronomy [Uppsala]
3 Department of Forensic Medicine [Stockholm]
4 DRACULA - Multi-scale modelling of cell dynamics : application to hematopoiesis
5 ICJ - Institut Camille Jordan
6 MMCS - Modélisation mathématique, calcul scientifique
7 Szpital Bielański [Warsaw]
8 MCPE - Medical Center of Postgraduate Education [Warsaw]
9 Bosch Institute [Sydney]
10 Cardiothoracic Surgery [Lund]
11 Medical University of Graz = Medizinische Universität Graz
12 EHB - European Homograft Bank [Bruxelles]
13 Stereology and Electron Microscopy Laboratory [Aarhus]
14 Spectrum Health [Grand Rapids]
15 Van Andel Institute [Grand Rapids]
16 Lund Stem Cell Center
Résumé
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.