Work on Reversing Scar Tissue in the Heart
A look at some of the research aimed at reversing the damage caused by heart attacks: "Our ultimate hope is that, during the acute period following myocardial infarction (MI), patients will be able to receive direct injections of factors that transform the existing fibroblast cells in the 'scar' into new myocytes. The resulting increase in muscle mass should help MI survivors to live more normal lives. ... When heart muscle cells become injured and die following an MI, patients have the major problem that these cells have little or no capacity for regeneration. ... Part of the process of remodelling that occurs following the injury is that fibroblast cells migrate to the site and create the scar. ... The process at first can be considered beneficial since without fibroblasts adding structural support damaged hearts would rupture. But later difficulties arise when the fibrotic scar doesn't contract like the muscle it has replaced. Reduced global contractility means the heart has to work much harder, and the extra stress can ultimately lead to heart failure and even death. ... One of the Holy Grails of cardiovascular research has been to replace these lost myocytes and return functionality to the heart. Some of the first approaches to be investigated were the introduction of stem or progenitor cells to the sites of injury. ... But many hurdles have been encountered including getting cells to integrate with neighbouring cells in the heart, and there have been concerns that residual 'rogue' cells could persist with the potential to keep dividing and give rise to tumours. Harnessing the vast reservoir of fibroblasts already present in the heart, we felt, could overcome many of these issues. They've the big advantage they're already present in the organ and closely integrated with neighbouring cells. ... the team were able to identify three [genes] Gata4, Mef2c, and Tbx5 that could convert fibroblasts taken from the hearts of adult mice into new myocytes. ... In the second part of the study, the team injected fibroblasts that already had the three genes inserted directly into the scar tissue of mice. They were able to show the fibroblasts differentiated into cardiomyocyte-like cells. ... The fibroblasts converted into cells with nice patterns of striations, typical of myocytes, and developed units that could generate force. ... In the latest study [they] have been able to take the process one step further by injecting a viral vector encoding the genes for Gata4, Mef2c, and Tbx5 directly into the scar tissue of mice who had just experienced an MI. ... With these studies we've obtained even better results showing that the fibroblasts become more like cardiomyocytes and functionally couple with their neighbours. They could beat in synchrony and improve the function of the heart."
Link: http://www.eurekalert.org/pub_releases/2012-04/esoc-tst032312.php