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Teams Identify Cardiac 'Stem Cell'

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Science  24 Nov 2006:
Vol. 314, Issue 5803, pp. 1225
DOI: 10.1126/science.314.5803.1225

Like many organs, the heart is a patchwork of cell types, from smooth muscle that pulses blood through arteries to endothelial cells lining vessels. These pieces, varied as they are, were long considered distant cousins born of different parent cells. But two new studies have uncovered a primitive type of heart cell in mice that can give rise to the heart's main cell lineages. If the finding holds up, it will make the heart one of very few organs, along with the blood, known to grow largely out of a single type of cell; it may also ease the introduction of embryonic stem cell treatments in cardiac patients.

“It's surprising that so much can come from” just one type of heart cell, says Timothy Kamp, who studies cardiovascular regenerative medicine at the University of Wisconsin, Madison. “You have essentially a type of cardiac stem cell.”

Although they took different approaches, the two groups that found the heart progenitor cells both identified overlapping genetic markers to define their progenitor population, and both found that the cells could differentiate into cardiac muscle and blood vessel cells, the principal building blocks of the heart. The first paper, led by Gordon Keller, a stem cell biologist at Mount Sinai School of Medicine in New York City, was published earlier this month in Developmental Cell; the second appeared this week in Cell. That work was led by a husband-and-wife team, Karl-Ludwig Laugwitz and Alessandra Moretti, at the Technical University of Munich in Germany, and Kenneth Chien at Massachusetts General Hospital in Boston.


The same cells from an early mouse embryo give rise to the heart's endothelial cells (red) in blood vessels, contracting heart muscle cells (green), and smooth muscle cells (blue, right image).


The Chien team found that mouse embryonic stem cells developing into heart cells first entered an intermediate state that could be monitored by tracking expression of three different genes. Those intermediates, which the scientists called “triple positive cells,” gave rise only to heart cells. To confirm that these triple positive progenitor cells, grown under artificial conditions, exist in an animal, the researchers examined mouse embryos at different points in their development. Around day 8, they detected them.

Although Keller's team did not use all the same markers as Chien's to characterize the cells it found, both groups found that their cells could differentiate into the same cardiovascular cell types. “We're arriving at a similar progenitor,” says Keller, also adding that “it's still pretty early days.”

To prove that these progenitor cells can become functioning, specialized heart cells, the scientists need to inject them back into an animal to see whether they give rise to the different cardiac tissue types, Moretti notes. That is also a key experiment to determine whether these master ancestor cells can repair a damaged heart. Keller's group has begun precisely this experiment, inserting the progenitor cells it identified into mice whose hearts resemble those of humans following a heart attack.

Chien notes that “we have not formally proven that that cell can make a whole heart.” Still, says Kamp, the work could ease one of the most worrying concerns about using embryonic stem cells in patients: that, left alone to form whatever cell type they fancy, they'll develop into tumors. “If you can have a more committed cell population that can only give rise to limited progeny,” Kamp says, “that's going to dramatically reduce the risk.” And the cells might still be flexible enough to form, say, a coronary artery, which includes different cell types. Still, admits Laugwitz, that “remains to be proven.” Both groups, in the United States and Germany, are working with human embryonic stem cells to see whether the mouse patterns will hold.

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