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Growth-factor-mediated cardiac stem cell activation in myocardial regeneration

Nature Clinical Practice Cardiovascular Medicine volume 4, pages S46–S51 (2007)Cite this article

Abstract

The concept of an intrinsic regenerative capacity of the adult mammalian myocardium owing to the presence of cardiac stem cells (CSCs) in the atria and ventricles is starting to be accepted by the cardiovascular research community. The identification of this cell population has improved the prospects for developing successful clinical protocols for human myocardial regeneration. In the normal adult myocardium, only a small fraction of CSCs undergo amplification and differentiation to replace the parenchymal cells lost by normal wear and tear. Physiological or pathological stimuli cause substantial activation of CSCs, which is mediated by a paracrine feedback loop between myocytes and CSCs. In response to stress, the myocytes produce growth factors and cytokines, for which CSCs have receptors, and autocrine, self-sustaining activation of growth-factor production is simultaneously triggered in the CSCs. These findings from human and animal studies led us to test whether in situ activation of CSCs by growth factors would be as effective as transplantation of CSCs into the regenerating myocardium after ischemia in an animal model that has relevance to humans. In a porcine model, we produced extensive and functionally relevant myocardial regeneration. Here, we discuss the properties of endogenous myocardial stem cells that might be exploited to produce clinical myocardial regeneration without the need for cell transplantation.

Key Points

  • The adult mammalian heart exhibits a substantial regenerative capacity, which is derived from resident cardiac stem cells (CSCs)

  • Physiological or pathological stimuli cause substantial activation of CSCs that participate in myocardial remodeling

  • Activation of CSCs during adaptation of the heart to stress is mediated by a paracrine–autocrine feedback loop between myocytes and CSCs

  • In situ activation of CSCs by growth factors in a porcine model, which has relevance to humans, is as effective as transplantation of CSCs into the regenerating myocardium after ischemia

  • The properties of endogenous myocardial stem cells can be exploited to produce myocardial regeneration without the need for cell transplantation

  • For meaningful myocardial regeneration to occur, clinical trials using CSCs must be derived from solid, clean, and reproducible basic science data

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Figure 1: Stereotypical response of cardiomyocytes to stress
Figure 2: Cardiac stem cells possess receptors for insulin-like growth factor 1
Figure 3: Cardiac stem cells possess receptors for hepatocyte growth factor

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Authors and Affiliations

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

    Daniele Torella

  2. GM Ellison and I Karakikes are postdoctoral fellows, and B Nadal-Ginard is Senior Investigator in the Cardiovascular Institute at the Mount Sinai School of Medicine, New York, NY, USA.,

    Georgina M Ellison, Ioannis Karakikes & Bernardo Nadal-Ginard

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

    Daniele Torella & Georgina M Ellison

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

    Bernardo Nadal-Ginard

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

Correspondence to Bernardo Nadal-Ginard.

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The authors declare no competing financial interests.

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Torella, D., Ellison, G., Karakikes, I. et al. Growth-factor-mediated cardiac stem cell activation in myocardial regeneration. Nat Rev Cardiol 4 (Suppl 1), S46–S51 (2007). https://doi.org/10.1038/ncpcardio0772

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  • DOI: https://doi.org/10.1038/ncpcardio0772

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