In the 2010 Cell paper, working in a Petri dish, the team were able to identify three of these 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 indispensible," explained Srivastava.
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," he said.
In the latest study (currently in press), Srivastava explained, 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," he said.
The team have also shown that fibroblasts taken from the skin of mice (dermal fibroblasts) can be converted into muscle-like cells. "Such data suggests fibroblasts throughout the body have the potential to be transformed, which means that similar approaches, using different factors, could be used to regenerate nerve cells for patients with spinal cord injuries and other cells for diabetic patients," said Srivastava.
For MI treatment, said Srivastava, the next step will be to test the direct injection approach in a larger animal, such as a pig, whose hearts are similar in size to humans. But a big question remains w
|Contact: ESC Press Office|
European Society of Cardiology