Inflammation and cell-based therapies to heal the damaged heart

Finding new approaches to treat the infarcted heart remains a biomedical and clinical challenge. In order to substitute dead or damaged myocardium for new, functional ones, a great variety of stem/progenitor cell-based experimental therapies have been tested. While none of the cell-based strategies so far tested correlate with a significant increase of cardiomyocytes, several studies have proven that these interventions improve heart function. Although it has been long suspected that this functional improvement could be secondary to natural cardiac reparative phenomena, no systematic study was available on this topic.  In a recent article, Bagnozzi and colleagues show that the acute immune response following myocardial infarction is the the effector of this functional improvement. In particular, these researchers provide a series of interesting data confirming that the infarcted heart activates an acute sterile immune response whose main characteristic is the temporal and regional induction of CCR2+ and CX3CR1+ macrophages. Using intracardiac injection of two distinct types of adult stem cells, as well as cells killed by freezing and thawing or a chemical inducer of the innate immune response, Bagnozzi and colleagues demonstrates that the heart always responds to these manipulation by accumulating CCR2+ and CX3CR1+ macrophages. Such cells are considered to underlie cardiac rejuvenation through the modulation of the border zone extracellular matrix, leading to a significant enhancement of heart function. This study strongly suggests a re-evaluation of current experimental cell-based therapies to treat the damaged heart, and emphasises the crucial role played by inflammation in post-myocardial ventricular remodelling.