Dynamics of Cell Generation and Turnover in the Human Heart

Olaf Bergmann; Sofia Zdunek; Anastasia Felker; Mehran Salehpour; Kanar Alkass; Samuel Bernard; Staffan L Sjostrom; Mirosława Szewczykowska; Teresa Jackowska; Cris Dos Remedios; Torsten Malm; Michaela Andrä; Ramadan Jashari; Jens R Nyengaard; Göran Possnert; Stefan Jovinge; Henrik Druid; Jonas Frisén

doi:10.1016/j.cell.2015.05.026

Dynamics of Cell Generation and Turnover in the Human Heart

Cell. 2015 Jun 18;161(7):1566-75. doi: 10.1016/j.cell.2015.05.026. Epub 2015 Jun 11.

Authors

Olaf Bergmann¹, Sofia Zdunek², Anastasia Felker², Mehran Salehpour³, Kanar Alkass⁴, Samuel Bernard⁵, Staffan L Sjostrom², Mirosława Szewczykowska⁶, Teresa Jackowska⁷, Cris Dos Remedios⁸, Torsten Malm⁹, Michaela Andrä¹⁰, Ramadan Jashari¹¹, Jens R Nyengaard¹², Göran Possnert³, Stefan Jovinge¹³, Henrik Druid¹⁴, Jonas Frisén¹⁵

Affiliations

¹ Department of Cell and Molecular Biology, Karolinska Institute, 171 77 Stockholm, Sweden. Electronic address: olaf.bergmann@ki.se.
² Department of Cell and Molecular Biology, Karolinska Institute, 171 77 Stockholm, Sweden.
³ Division of Ion Physics, Department of Physics and Astronomy, Uppsala University, 751 20 Uppsala, Sweden.
⁴ Department of Cell and Molecular Biology, Karolinska Institute, 171 77 Stockholm, Sweden; Department of Forensic Medicine, Karolinska Institute, 171 77 Stockholm, Sweden.
⁵ Department of Mathematics, Institut Camille Jordan, Université de Lyon, 69622 Villeurbanne Cedex, France.
⁶ Department of Pediatrics, Bielanski Hospital, 01-809 Warsaw, Poland.
⁷ Department of Pediatrics, Bielanski Hospital, 01-809 Warsaw, Poland; Department of Pediatrics, Medical Center of Postgraduate Education, 01-813 Warsaw, Poland.
⁸ Discipline of Anatomy, Bosch Institute, University of Sydney, Sydney, NSW 2006, Australia.
⁹ Department of Paediatric Cardiac Surgery, Skåne University Hospital, 221 85 Lund, Sweden.
¹⁰ Klinikum Klagenfurt & Section for Surgical Research, Department of Cardiothoracic and Vascular Surgery, Medical University Graz, 9020 Graz, Austria.
¹¹ European Homograft Bank, 1120 Brussels, Belgium.
¹² Stereology and Electron Microscopy Laboratory, Centre for Stochastic Geometry and Advance Bioimaging, Aarhus University, 8000 Aarhus, Denmark.
¹³ Spectrum Health Frederik Meijer Heart & Vascular Institute, Grand Rapids, MI 49503, USA; Van Andel Institute, Grand Rapids, MI 49503, USA; Stem Cell Center, Lund University, 221 84 Lund, Sweden.
¹⁴ Department of Forensic Medicine, Karolinska Institute, 171 77 Stockholm, Sweden.
¹⁵ Department of Cell and Molecular Biology, Karolinska Institute, 171 77 Stockholm, Sweden. Electronic address: jonas.frisen@ki.se.

PMID: 26073943
DOI: 10.1016/j.cell.2015.05.026

Abstract

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 (14)C 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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Endothelial Cells / cytology
Heart / physiology
Humans
Leukocyte Common Antigens / metabolism
Mesoderm / cytology
Myocardium / cytology
Myocytes, Cardiac / cytology*
Polyploidy
Radiometric Dating

Substances

Leukocyte Common Antigens
PTPRC protein, human