In order to bring you the best possible user experience, this site uses Javascript. If you are seeing this message, it is likely that the Javascript option in your browser is disabled. For optimal viewing of this site, please ensure that Javascript is enabled for your browser.
Did you know that your browser is out of date? To get the best experience using our website we recommend that you upgrade to a newer version. Learn more.

Unravelling the mechanisms of action of cardiac stem-cell therapy

Commented by Ricardo Sanz Ruiz, MD, PhD.

Stem Cells, Cell Cycle, Cell Senescence, Cell Death

Now that we face in the field of Cardiovascular Reparative Medicine a time of reflection and careful thinking and planning of future directions, another work has been published which denies the relevant contribution of exogenous stem cells to increase the pool of functional cardiomyocytes in a rodent model of myocardial ischemia/reperfusion. The authors investigated the mechanism of action of intracardiac injections of fractioned bone marrow mononuclear cells and cardiac progenitor cells by comparing it to the one of a non-cellular activator of the innate immune response (zymosan). All these products improved cardiac function to the same extent, by inducting a CCR2+ and CX3CR1+ macrophage-based response, but not by producing new beating myocardial cells. Benefits of this acute immune response included modifications of the fibroblast activity, a reduction of the extracellular matrix formation and an improvement in the mechanical properties of the scar border zone. This work sheds light on important cellular and immunological pathways to target with future reparative products.  


  1. Fernandez-Aviles, F. et al. Global position paper on cardiovascular regenerative medicine. Eur Heart J 38, 2532-2546, (2017).
  2. Eschenhagen, T. et al. Cardiomyocyte Regeneration: A Consensus Statement. Circulation 136, 680-686, (2017).
  3. Bajpai, G. et al. Tissue Resident CCR2- and CCR2+ Cardiac Macrophages Differentially Orchestrate Monocyte Recruitment and Fate Specification Following Myocardial Injury. Circ Res 124, 263-278, (2019).
  4. Jung, S. et al. Analysis of fractalkine receptor CX(3)CR1 function by targeted deletion and green fluorescent protein reporter gene insertion. Mol Cell Biol 20, 4106-4114 (2000).
  5. Dick, S. A. et al. Self-renewing resident cardiac macrophages limit adverse remodeling following myocardial infarction. Nat Immunol 20, 29-39, (2019).
The content of this article reflects the personal opinion of the author/s and is not necessarily the official position of the European Society of Cardiology.

Contact us

ESC Working Group on Cardiovascular Regenerative and Reparative Medicine

European Society of Cardiology

European Heart House
Les Templiers
2035 Route des Colles
CS 80179 Biot

06903, Sophia Antipolis, FR

Tel: +