Mice lack stem cells in the heart needed for self-repair

There’s some bad news for people who have suffered heart attacks: Healing may not come from within.

Researchers have debated for years whether hearts have their own stem cells. If they existed, those cells could produce new heart muscle cells and might help the organ repair itself after injury. Now that debate may finally be over. After following the fate of dividing cells in the hearts of mice, researchers have concluded that there are no heart stem cells.

Instead, heart attacks and other injuries to the organ signal immune cells and scar-forming cells called fibroblasts to divide and attempt to close the wound, the team reports online December 7 in the Proceedings of the National Academy of Sciences. Human hearts probably also lack stem cells, evidence suggests.

“This study is fairly definitive that there is not a population of stem cells within the heart that gives rise to new muscle,” says Deepak Srivastava, a cardiologist and developmental biologist at the Gladstone Institutes in San Francisco who was not involved in the study.

Other researchers agree the study seems to settle the matter. “It can certainly seem like this is a letdown,” says Ronald Vagnozzi, a cardiac cell biologist at Cincinnati Children’s Hospital. On the bright side, “this paper is a rich resource of information” that may help scientists better understand what happens in the heart during development and after a heart attack, he says. That knowledge may help researchers limit heart attack damage.

Scientists thought the heart might have stem cells because previous research indicated that a small number of heart muscle cells are made throughout life, says Hans Clevers, a stem cell biologist at Hubrecht Institute in Utrecht, the Netherlands, who led the new study. Still, only about 1 percent or less of heart muscle cells get replaced, according to research measuring the cells for carbon 14 released from Cold War–era nuclear bomb tests (SN: 4/25/09, p. 11). Measuring levels of carbon 14 in people who were born before the bombs went off can tell researchers how often the new cells are made.

But exactly where those new muscle cells come from was a mystery. Scientists had three major theories — that the new heart cells are born from stem cells within the organ itself, that the cells are born from stem cells that enter the blood from elsewhere in the body and integrate into the heart, or that heart muscle cells can divide and produce more of themselves.

Clevers’ group created mice in which dividing cells in the heart make a red fluorescent protein that allowed researchers to track the cells. Then, the team analyzed which genes were turned on in those cells to figure out their identities. There was no evidence of stem cells, and only already existing heart muscle cells, called cardiomyocytes, made new muscle cells.

But those heart muscle cells divided and made new cells infrequently; only 11 of about 8 million cardiomyocytes were caught dividing in 1.5-year-old mice. That rate didn’t improve after a heart attack, something scientists thought might happen if the heart had reason to repair itself. After an injury, “you come back one month, two months, a year later, but you see not a single new cardiomyocyte,” Clevers says.

Instead, rapidly dividing immune cells flood into the site of the injury, accompanied by dividing fibroblasts, which make connective tissue and create a scar over a wound. Understanding the scarring process may lead to ways to limit heart attack damage, Clevers says, but he doubts that the heart can repair itself.

Heart self-repair may not be a lost cause, Srivastava says. He and colleagues are working on ways to coax heart muscle cells to produce more of themselves.