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Cardiac stem cells: isolation, expansion and experimental use for myocardial regeneration


Cellular cardiomyoplasty (myogenic cell grafting) is actively being explored as a novel method to regenerate damaged myocardium. The adult human heart contains small populations of indigenous committed cardiac stem cells or multipotent cardiac progenitor cells, identified by their cell-surface expression of c-kit (the receptor for stem cell factor), P-glycoprotein (a member of the multidrug resistance protein family), and Sca-1 (stem cell antigen 1, a mouse hematopoietic stem cell marker) or a Sca-1-like protein. Cardiac stem cells represent a logical source to exploit in cardiac regeneration therapy because, unlike other adult stem cells, they are likely to be intrinsically programmed to generate cardiac tissue in vitro and to increase cardiac tissue viability in vitro. Cardiac stem cell therapy could, therefore, change the fundamental approach to the treatment of heart disease.

Key Points

  • Use of flow cytometry to sort cells with specific surface markers allows the identification of defined cell populations with an inducible differentiated phenotype and the potential for cardiac regeneration

  • Clinical translation of sorted stem cells, however, requires improved recruitment and induction by growth factors and cytokines

  • Isolation of cardiac stem cells by exploiting their functional properties (migration capacity, three-dimensional growth in culture) allows the expansion of a heterogeneous and spontaneously differentiating cell population from a very small sample

  • Clinical translation requires the isolation of cardiac stem cells from surgical or biopsy samples, ex vivo expansion, and reinjection into the damaged heart for autologous cell cardiomyoplasty

  • The three-dimensional self-organization of the cardiac stem cells in culture, comprising a core of proliferating progenitor cells protected by external layers of more-differentiated cells, allows a physiologic relationship between the cells and their environment

  • The three-dimensional organization of the cardiac stem cells could improve their survival and engraftment, once injected into the damaged heart

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Figure 1: Morphology of the isolated human cardiospheres
Figure 2: Phenotype of the isolated human cardiospheres


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This study was supported by a grant from the Ministero della Pubblica Istruzione, Università e Ricerca (MIUR) and by a grant from the Istituto Pasteur-Fondazione Cenci Bolognetti to the Department of Experimental Medicine, University of Rome “La Sapienza”.

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Correspondence to Alessandro Giacomello.

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Barile, L., Chimenti, I., Gaetani, R. et al. Cardiac stem cells: isolation, expansion and experimental use for myocardial regeneration. Nat Rev Cardiol 4 (Suppl 1), S9–S14 (2007).

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