title: Dynamics of Cell Generation and Turnover in the Human Heart.
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.
authors.affiliation: Department of Cell and Molecular Biology, Karolinska Institute, 171 77 Stockholm, Sweden. Electronic address: olaf.bergmann@ki.se.
authors.forename: Olaf
authors.initials: O
authors.lastname: Bergmann
authors.affiliation: Department of Cell and Molecular Biology, Karolinska Institute, 171 77 Stockholm, Sweden.
authors.forename: Sofia
authors.initials: S
authors.lastname: Zdunek
authors.affiliation: Department of Cell and Molecular Biology, Karolinska Institute, 171 77 Stockholm, Sweden.
authors.forename: Anastasia
authors.initials: A
authors.lastname: Felker
authors.affiliation: Division of Ion Physics, Department of Physics and Astronomy, Uppsala University, 751 20 Uppsala, Sweden.
authors.forename: Mehran
authors.initials: M
authors.lastname: Salehpour
authors.affiliation: Department of Cell and Molecular Biology, Karolinska Institute, 171 77 Stockholm, Sweden; Department of Forensic Medicine, Karolinska Institute, 171 77 Stockholm, Sweden.
authors.forename: Kanar
authors.initials: K
authors.lastname: Alkass
authors.affiliation: Department of Mathematics, Institut Camille Jordan, Université de Lyon, 69622 Villeurbanne Cedex, France.
authors.forename: Samuel
authors.initials: S
authors.lastname: Bernard
authors.affiliation: Department of Cell and Molecular Biology, Karolinska Institute, 171 77 Stockholm, Sweden.
authors.forename: Staffan L
authors.initials: SL
authors.lastname: Sjostrom
authors.affiliation: Department of Pediatrics, Bielanski Hospital, 01-809 Warsaw, Poland.
authors.forename: Mirosława
authors.initials: M
authors.lastname: Szewczykowska
authors.affiliation: Department of Pediatrics, Bielanski Hospital, 01-809 Warsaw, Poland; Department of Pediatrics, Medical Center of Postgraduate Education, 01-813 Warsaw, Poland.
authors.forename: Teresa
authors.initials: T
authors.lastname: Jackowska
authors.affiliation: Discipline of Anatomy, Bosch Institute, University of Sydney, Sydney, NSW 2006, Australia.
authors.forename: Cris
authors.initials: C
authors.lastname: Dos Remedios
authors.affiliation: Department of Paediatric Cardiac Surgery, Skåne University Hospital, 221 85 Lund, Sweden.
authors.forename: Torsten
authors.initials: T
authors.lastname: Malm
authors.affiliation: Klinikum Klagenfurt & Section for Surgical Research, Department of Cardiothoracic and Vascular Surgery, Medical University Graz, 9020 Graz, Austria.
authors.forename: Michaela
authors.initials: M
authors.lastname: Andrä
authors.affiliation: European Homograft Bank, 1120 Brussels, Belgium.
authors.forename: Ramadan
authors.initials: R
authors.lastname: Jashari
authors.affiliation: Stereology and Electron Microscopy Laboratory, Centre for Stochastic Geometry and Advance Bioimaging, Aarhus University, 8000 Aarhus, Denmark.
authors.forename: Jens R
authors.initials: JR
authors.lastname: Nyengaard
authors.affiliation: Division of Ion Physics, Department of Physics and Astronomy, Uppsala University, 751 20 Uppsala, Sweden.
authors.forename: Göran
authors.initials: G
authors.lastname: Possnert
authors.affiliation: 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.
authors.forename: Stefan
authors.initials: S
authors.lastname: Jovinge
authors.affiliation: Department of Forensic Medicine, Karolinska Institute, 171 77 Stockholm, Sweden.
authors.forename: Henrik
authors.initials: H
authors.lastname: Druid
authors.affiliation: Department of Cell and Molecular Biology, Karolinska Institute, 171 77 Stockholm, Sweden. Electronic address: jonas.frisen@ki.se.
authors.forename: Jonas
authors.initials: J
authors.lastname: Frisén
mesh_terms: D042783:Endothelial Cells / Q000166:cytology; D006321:Heart / Q000502:physiology; D006801:Humans; D017493:Leukocyte Common Antigens / Q000378:metabolism; D008648:Mesoderm / Q000166:cytology; D009206:Myocardium / Q000166:cytology; D032383:Myocytes, Cardiac / Q000166:cytology*; D011123:Polyploidy; D055110:Radiometric Dating
chemical_list: D017493:Leukocyte Common Antigens; C516769:PTPRC protein, human