Researchers Stumble upon New Source of Heart Stem Cells

Today in the United States, congestive heart failure, the ineffective pumping of the heart caused by the loss or dysfunction of heart muscle cells, afflicts 4.8 million people, with 400,000 new cases each year. One of the major contributors to the development of this condition is a heart attack, known medically as a myocardial infarction, which occurs in nearly 1.1 million Americans each year. Despite advances in surgical procedures, mechanical assistance devices, drug therapy, and organ transplantation, more than half of patients with congestive heart failure die within five years of initial diagnosis. For those suffering from heart disease, stem cell biology represents a new medical frontier; one working toward using stem cells to replace damaged heart cells and literally restore cardiac function.

In 2006, scientists identified a cardiac stem cell, marked by the expression of a gene called Nkx2-5, with the potential to become either heart muscle or cells lining blood vessels in the organ's left-sided chambers. Simultaneously, other U.S. researchers discovered a related progenitor heart cell, so-called because of its capacity to generate different types of tissue that produces the same cell types in the right-sided heart chambers.

Most recently, quite by accident, U.S. researchers discovered a new group of stem cells that may one day play a critical role in the regeneration of injured heart tissue. Located in the outermost layer of the heart, these stem cells can give rise to heart muscle cells, known as cardiomyocytes. "In heart failure, you lose cardiomyocytes, so the only way to reverse heart failure is to make more of these cells," said William Pu, the study's lead researcher and a pediatric cardiologist at Children's Hospital in Boston, Massachusetts.

While studying the role of a different gene in the heart's outer lining, called the epicardium, Dr. Pu and colleagues labeled cells in live mouse embryos with red fluorescent protein. "Unexpectedly, we saw that these epicardial cells were becoming cardiomycytes-it was a lucky observation," said Pu. The researchers showed that the cells can not only metamorphose into cardiomycytes, but also into smooth muscle cells, endothelial cells, which line the interior of blood vessels, and fibroblasts, found in connective tissue. The results were independently verified by another team of scientists at the University of California in San Diego.

Pu's findings show that new heart stem cells can also be derived from a third type of cardiac stem cell, located within the surface of the organ and identifiable through its expression of a gene called Wt1. Gene expression is the process by which information encoded in the DNA of a particular gene is transformed into a protein or RNA, which plays a key role in protein synthesis.

Pu said the next challenge is trying to figure out how a progenitor stem cell decides to become a certain type of functioning cell within the heart, and then how to develop methods to trick the stem cells into transforming into the desired tissue. "We still don't know how we can manipulate these progenitors," he said.

Both Pu's and the corroborating study were published on June 22 in the online journal Nature.