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Myocyte death and renewal: modern concepts of cardiac cellular homeostasis

Nature Clinical Practice Cardiovascular Medicine volume 4, pages S52–S59 (2007)Cite this article

Abstract

The adult mammalian myocardium has a robust intrinsic regenerative capacity because of the presence of cardiac stem cells (CSCs). Despite being mainly composed of terminally differentiated myocytes that cannot re-enter the cell cycle, the heart is not a postmitotic organ and maintains some capacity to form new parenchymal cells during the lifespan of the organism. Myocyte death and formation of new myocytes by the CSCs are the two processes that enable this organ to maintain a proper and uninterrupted cardiac output from birth to adulthood and into old age. CSCs are activated in response to pathological or physiological stimuli, whereby they enter the cell cycle and differentiate into new myocytes (and vessels) that significantly contribute to changes in myocardial mass. The future of regenerative cardiovascular medicine is arguably dependent on our success in dissecting the biology and mechanisms regulating the number, growth, differentiation, and aging of CSCs. This information will generate the means to manipulate CSC growth, survival, and differentiation and, therefore, will provide the tools for the design of more physiologically relevant clinical regeneration protocols. In this article, we review the developments in cardiac cell biology that might, in our opinion, have a broad impact on cardiovascular medicine.

Key Points

  • Cardiac stem cells (CSCs) enable the heart to have the capacity to form new parenchymal cells during the lifespan of the organism; the heart is no longer considered a postmitotic organ

  • Myocyte death and the formation of new myocytes by CSCs enable the heart to maintain a proper and uninterrupted cardiac output from birth to adulthood and into old age

  • The adult heart harbors a 'true' CSC population, which is Oct-4pos, exhibits primitive characteristics, possesses 'stemness' genes, and is pluripotent

  • CSCs are activated, enter the cell cycle, and differentiate into new myocytes and blood vessels that significantly contribute to changes in myocardial mass during physiological or pathologic remodeling

  • The success of future physiologically relevant clinical regeneration protocols will require solid basic science data regarding the molecular biology and mechanisms regulating the number, growth, differentiation, and aging of CSCs

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Figure 1: Schematic representation of the transitional sequence of cardiac-stem-cell-committed progeny
Figure 2: The true cardiac stem cell

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Authors and Affiliations

  1. GM Ellison and I Karakikes are postdoctoral fellows and B Nadal-Ginard is a senior investigator in the Cardiovascular Institute and Center for Cardiovascular Health at the Mount Sinai School of Medicine, New York, NY, USA.,

    Georgina M Ellison, Ioannis Karakikes & Bernardo Nadal-Ginard

  2. Division of Cardiology, Department of Experimental and Clinical Medicine at the Magna Graecia University, D Torella is an assistant professor in the Laboratory of Molecular and Cellular Cardiology, Catanzaro, Italy.,

    Daniele Torella

  3. GM Ellison is also a postdoctoral fellow and D Torella is a senior lecturer in the Laboratory of Molecular and Cellular Physiology, The Research Institute for Sport and Exercise Sciences at the Liverpool John Moores University, Liverpool, UK.,

    Georgina M Ellison & Daniele Torella

  4. B Nadal-Ginard is also Head of Research at the Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid, Spain.,

    Bernardo Nadal-Ginard

Authors
  1. Georgina M Ellison
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  2. Daniele Torella
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  3. Ioannis Karakikes
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  4. Bernardo Nadal-Ginard
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Correspondence to Bernardo Nadal-Ginard.

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The authors declare no competing financial interests.

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Ellison, G., Torella, D., Karakikes, I. et al. Myocyte death and renewal: modern concepts of cardiac cellular homeostasis. Nat Rev Cardiol 4 (Suppl 1), S52–S59 (2007). https://doi.org/10.1038/ncpcardio0773

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