A diseased mammalian embryonic heart boosts its production of heart muscle cells to spur its own regeneration, according to a study appearing tomorrow in Developmental Cell.

"The mammalian heart has a phenomenal capacity to fix itself," Timothy Cox at the University of Washington, the study's lead author, told The Scientist, "which is important [since there are] lots of insults during embryogenesis."

Researchers knew that cardiomyocytes could regenerate in the injured fetal hearts of creatures such as amphibians, but the effect had not been previously shown in mammals. The new study shows that the mammalian heart can regenerate heart cells even if half of its cardiomyocytes are diseased.

"What's new here is they show in a diseased heart an increased rate of proliferation, which in effect repairs the heart," Michael Parmacek, director of the Penn Cardiovascular Institute at the University of Pennsylvania School of Medicine, who was not involved in the study, told The Scientist.

Cox and his colleagues developed a mouse knockout model to emulate cardiomyopathy in the embryonic hearts. The team used a reporter transgene with a fluorescent protein to inactivate the gene encoding a crucial enzyme for the production of metabolic heme proteins. Without the enzyme, cardiomyocytes malfunction. Because the gene is X-linked, only female knockouts survive, since they maintain about 50% expression of the gene on their second chromosome. Half of the cells in the knockout hearts were diseased.

The researchers counted the fluorescent cells to record the quantity of diseased tissue in each fetal heart. They then tracked those cells and found only 10% diseased tissue at birth, while showing about a 27% increase in proliferating myocardial cells.

The fetal mouse hearts were able to regenerate new tissue around the diseased cells and develop fully-functional hearts. However, once the mice grew up, many died prematurely and others had an entire array of cardiac disorders, showing that the embryonic regeneration does not get rid of the diseased cells completely. Instead, said Parmacek, the normal regenerative ability of embryonic cardiomyocytes is increased in the presence of diseased cells. The next step, said Cox, is to identify the signals that turn on the increased proliferation.

"It's a really good model and to some extent has relevance to human cardiomyopathy," added Parmacek, since cardiomyopathies do occur in humans as a result of malfunctioning metabolic processes. "A whole number of [metabolic] cardiomyopathies actually exist, so [the paper has] interesting relevance and translational insights that many of the models don't have."