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Cardiac primitive cells become committed to a cardiac fate in adult human heart with chronic ischemic disease but fail to acquire mature phenotype: genetic and phenotypic study

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Abstract

Adult human heart hosts a population of cardiac primitive CD117-positive cells (CPCs), which are responsible for physiological tissue homeostasis and regeneration. While the bona fide stem cells express telomerase, their progenies are no longer able to preserve telomeric DNA; hence the balance between their proliferation and differentiation has to be tightly controlled in order to prevent cellular senescence and apoptosis of CPCs before their maturation can be accomplished. We have examined at cellular and molecular level the proliferation, apoptosis and commitment of CPCs isolated from normal (CPC-N) and age-matched pathological adult human hearts (CPC-P) with ischemic heart disease. In the CPC-P, genes related to early stages of developmental processes, nervous system development and neurogenesis, skeletal development, bone and cartilage development were downregulated, while those involved in mesenchymal cell differentiation and heart development were upregulated, together with the transcriptional activation of TGFβ/BMP signaling pathway. In the pathological heart, asymmetric division was the prevalent type of cardiac stem cell division. The population of CPC-P consisted mainly of progenitors of cardiac cell lineages and less precursors; these cells proliferated more, but were also more susceptible to apoptosis with respect to CPC-N. These results indicate that CPCs fail to reach terminal differentiation and functional competence in pathological conditions. Adverse effects of underlying pathology, which disrupts cardiac tissue structure and composition, and cellular senescence, resulting from cardiac stem cell activation in telomere dysfunctional environment, can be responsible for such outcome.

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Acknowledgments

This work was partially supported by the Future in Research (Futuro in Ricerca) program of the Italian Ministry of Education, University and Research (Ministero dell’Istruzione, dell’Università e della Ricerca), grant RBFR10L0GK (University of Naples “Federico II”).

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The authors declare that they have no conflict of interests.

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Authors and Affiliations

  1. Department of Biomorphological and Functional Sciences, University of Naples “Federico II”, via S. Pansini 5, Bldg 20, Room 207, 80131, Naples, Italy

    Daria Nurzynska, Franca Di Meglio, Veronica Romano, Rita Miraglia, Anna Maria Sacco, Francesca Latino, Stefania Montagnani & Clotilde Castaldo

  2. Department of Cardiothoracic Sciences, Second University of Naples, Naples, Italy

    Ciro Bancone & Alessandro Della Corte

  3. Department of Cardiovascular Surgery and Transplants, V. Monaldi Hospital, Naples, Italy

    Ciro Maiello & Cristiano Amarelli

Authors
  1. Daria Nurzynska
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  2. Franca Di Meglio
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  4. Rita Miraglia
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  5. Anna Maria Sacco
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  9. Ciro Maiello
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  11. Stefania Montagnani
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  12. Clotilde Castaldo
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Corresponding authors

Correspondence to Daria Nurzynska or Clotilde Castaldo.

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D. Nurzynska, F. Di Meglio and C. Castaldo contributed equally to this work.

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Nurzynska, D., Di Meglio, F., Romano, V. et al. Cardiac primitive cells become committed to a cardiac fate in adult human heart with chronic ischemic disease but fail to acquire mature phenotype: genetic and phenotypic study. Basic Res Cardiol 108, 320 (2013). https://doi.org/10.1007/s00395-012-0320-2

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  • DOI: https://doi.org/10.1007/s00395-012-0320-2

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