Researchers at Children's Hospital Boston say they have pinpointed a new, previously unrecognized group of stem cells located in the surface of the heart that give rise to heart muscle cells (cardiomyocytes), advancing the hope of being able to regenerate injured heart tissue.

"There's a lot of interest in finding places to obtain new cardiomyocytes, because in heart failure, you lose cardiomyocytes, so the only way to reverse heart failure is to make more of these cells," said William Pu, M.D., a pediatric cardiologist at Children's who was the study's senior investigator.

Although epicardial cells are known to give rise to smooth muscle and endothelial cells during coronary vessel formation, nobody previously thought that epicardial cells might turn into cardiomyocytes.

"I couldn't believe it at first, myself," said Bin Zhou, MD, a research fellow in Pu's laboratory and the study's first author.

Previously, the Children's team found a specific stem cell or progenitor, marked by expression of a gene called Nkx2-5, forms many components of the heart: heart muscle cells, vascular smooth muscle cells, and the endothelial cells lining blood vessels in the heart's left-sided chambers. The team at MGH found a related progenitor, marked by expression of the Isl1 gene, that produces these same cell-types in the right-sided heart chambers.

Now, researchers have shown that heart muscle cells can also be derived from a third type of cardiac progenitor, located within the epicardium and identifiable through its expression of a gene called Wt1.

Pu and Zhou tagged the Wt-1 expressing epicardial cells with a fluorescent red protein, then allowed the cells to differentiate. The image shows a descendent cardiomyocyte (green) that carries the same red marker, and another cell that arose from different origins. (The blue stain indicates cell nuclei). Credit: Bin Zhou, MD (Children's Hospital Boston)

The results were independently corroborated by researchers from the University of California, San Diego. Using a different genetic marker, Tbx18, the UCSD team also showed that cardiomyocytes can be derived from the epicardium, and their study will be published in the same issue of Nature.

(Agencies via Xinhua June 23, 2008)