Published online 2 April 2009 | Nature | doi:10.1038/news.2009.232

News

The cold war helps settle a hot debate about how hearts grow.

New cells in old hearts. Punchstock

Fallout from nuclear bomb tests during the cold war has just yielded encouraging news for those searching for ways to reverse heart disease.

A team led by Jonas Frisén from the Karolinska Institute in Stockholm has shown that adult human hearts make new muscle cells, albeit very, very slowly1.

Human heart cells that can generate cardiomyocytes in culture have been identified before. But how the heart regenerates naturally has been hotly contested, says Kenneth Chien of the Harvard Stem Cell Institute in Cambridge. "This study shows for the first time and very clearly that there is some turnover of cardiomyocytes within the lifetime of an individual." It also lays to rest claims that heart cells turn over quickly, says Deepak Srivastava of the Gladstone Institute of Cardiovascular Disease in San Francisco, California.

To conduct the study, Frisén created his own version of radiocarbon dating. After the Second World War, tests of nuclear bombs spewed carbon-14 pollution into the atmosphere. This isotope was incorporated into plants and the people who consumed them.

After above-ground tests were stopped in 1963, levels of the isotope started to fall. The 14C in a cell's DNA corresponds to the amount of the isotope in the atmosphere at the time it was dividing, providing a way to date a cell's birth. (Unlike in archaeology studies, the half-life of 14C, about 5,700 years, does not affect these results.)

Slow but steady

People born before 1955 — and before the most intense period of nuclear-bomb testing — had levels of 14C in their cardiomyocytes that were higher than was present in the atmosphere at the time of their birth, so some of these cells must have arisen later on in their lives. Further work and mathematical modelling allowed Frisén's team to calculate that a 50-year-old heart still contains more than half the cells it had at birth and that the turnover slows down with time. A 25-year-old heart replaces about 1% of all cardiomyocytes over a year; a 75-year-old about half that.

Even that speed might be enough to be useful for people with heart disease who need new cardiomyocytes, says Charles Murry, who studies cardiovascular medicine at the University of Washington in Seattle. "They do turn over a little bit, and if we can figure how that works, we can exploit it."

Frisén notes that some existing drugs cause organs to generate new cells. Erythropoeitin, for instance, causes new blood cells to form in the bone marrow. Certain antidepressants cause new neurons to form in the brain. "It's not completely science fiction to imagine pharmaceuticals that promote the production of new cardiomyocytes," he says.

The next step, says Frisén, is to study heart tissue from people who have had heart attacks to see whether the heart produces more cardiomyocytes after injury. If so, techniques that enhance that process could reverse heart damage.

Big bang?

But the carbon-dating strategy can't answer one crucial question: what type of cell produces the new cardiomyocytes? "Is it a large effect in a discrete population or a small effect in a large population?" asks Chien.

ADVERTISEMENT

That could make a huge difference in heart-repair strategies. If the regenerating cells contribute only to specialized parts of the heart, Chien says, then harnessing that potential to reverse heart disease will be much more difficult. He sees a different problem if the regenerative capacity is general. "It's so small it might be clinically trivial."

Murry agrees that the first step will be to find the source of the new cardiomyocytes. "Then we need to know what regulates them. What makes this process go at all?" After that, he says, researchers can try to get the cells to divide in situ or isolate them and try to expand the right population in culture. Even a small effect, he says, could mean a lot. "The animal data show that even a modest restoration of heart-muscle mass gives you a big bang for your buck."