April 5, 2012

Scar Tissue into Beating Hearts: A “Game Changer” Transformation

(Ivanhoe Newswire) -- New research reveals new developments to reprogram scar tissue, that is a result from myocardial infarction (MI), into heart muscle cells.  Scientists believe the new approach is a "game changer" with potential to revolutionise treatment of MI.

"Our ultimate hope is that, during the acute period following 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," Dr. Deepak Srivastava, study author and director of the Gladstone Institute of Cardiovascular Disease in San Fransisco, was quoted as saying.

Healthy heart tissue is a combination of several different kinds of cells, including those that provide beating muscle (cardiomyocytes) and provide architectural support to the myocytes (cardiac fibroblasts).

"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.  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 contractually means the heart has to work much harder, and the extra stress can ultimately lead to heart failure and even death," Dr. Srivastava was quoted as saying.

One of the most important aspects of cardiovascular research has typically been to replace the lost myocytes and return functionality to the heart.  The first approaches to be studied were the introduction of stem 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," Dr. Srivastava was quoted as saying.

Much of the focus of Dr. Srivastava's lab has been to spot genetic factors that are responsible for the formation of embryonic hearts.  Scientists then identified 14 key genes that were the major "on/off" switches for cardiac genetic programming.  They were able to identify three genes, Gata4, Mef2c, and Tbx5, that could convert fibroblasts taken from the hearts of adult mice into new myocytes.  "By removing each gene one at a time we were able to whittle things down to the three factors that were indispensable," Dr. Srivastava was quoted as saying.

In the second part of the study, scientists injected fibroblasts that already had the three genes into scar tissue in mice.  They were able to show the fibroblasts differentiated into cardiomyocyte-like cells.

In the latest study, Dr. Srivastava explained that they have been able to take the process one step further by injecting a viral vector encoding the genes into scar tissue in 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," Srivastava was quoted as saying.

SOURCE:  European Society of Cardiology, April 2012