Although the beneficial effects of cell therapy for myocardial regeneration after an infarction have lead to phase I clinical trials, the mechanism of the novel therapy is often questioned. Replacing the scar tissue with muscle cells and stimulating neo-vessel formation in the implanted area have been proposed. However, a number of studies recently demonstrated that the survival rate of implanted cells was too low and that number of implanted cells decreased with time after transplantation. The number of surviving cells may not be enough to form adequate new muscle tissue to repair the damaged myocardium.

We recently found that extracellular matrix in the myocardium plays an important role in maintaining the ventricular chamber size, and disruption of the matrix network may contribute to the apoptosis of cardiomyocytes leading to dilated cardiomyopathy. We implanted smooth muscle cells into the heart with dilated cardiomyopathy prior to ventricular dilatation. We found that implanted cells survived in the implanted area and altered myocardial matrix metabolism both within and remote from the region of implantation. Matrix metalloproteinase activity decreased in the transplanted group as compared with control group. The matrix structure was maintained and ventricular dilatation was prevented. These data suggest that implanted cells prevented ventricular dilatation through the alteration of matrix metabolism, which is a possible mechanism for implanted cells to improve heart function.