Published online 24 February 2011 | Nature | doi:10.1038/news.2011.123


Young mammal hearts heal themselves

Organs in baby mice can recover from damage that occurs in the first week of life.

heart cellsA regenerating heart 7 days post-injury. Green indicates cell division; red labels cardiomyocytes; blue stains DNA.Enzo Porrello

Staying young at heart has taken on a new meaning. Newborn mice can mend their own hearts, thanks to the replication of healthy cardiac cells. The findings, published today in Science1, reveal striking similarities in the way that fish and neonate mammals rejuvenate their organs.

Zebrafish (Danio rerio) can recover lost cardiac tissue throughout their life, even after a 20% amputation of the ventricle, in large part because of the proliferation of remaining heart muscle cells called cardiomyocytes2,3. Similarly, mouse embryos with a genetic defect that harms the heart can restore cardiac cells through proliferation and regain normal function4. Although adult mammals can replace some damaged cardiomyocytes, the turnover rate in humans is estimated to be lower than 1% a year — not enough to revitalize the organ after a heart attack or other major injury that causes scar formation5.

Follow your heart

Hesham Sadek, a cardiologist of the University of Texas Southwestern Medical Center in Dallas and lead author of the new study1, suspected that there might be a crucial stage during mammalian development after which cardiomyocytes are no longer capable of repopulating and repairing the heart.

So, he and his team surgically removed about 15% of muscle tissue in the walls of the left ventricle of 1-day-old mice. One week later, they found molecular evidence for cardiomyocyte proliferation throughout the heart. The animals fully recovered muscle tissue within three weeks of the operation, and their left ventricle pumped blood normally within two months. The same procedure performed on 7-day-old mice did not lead to cardiomyocyte proliferation or regeneration.

The mice were genetically engineered to express a blue tint in their cardiomyocytes, so the researchers were able to determine whether cells from this lineage permeated the new tissue. They found that most of the new cardiomyocytes came from pre-existing cardiac cells rather than from stem cells, although they cannot completely rule out the role of stem cells in some types of cardiac repair.

Genetic off-switch


The study "narrows the window during which the transition is made from a regenerative heart to a non-regenerative structure", says Kenneth Poss, a cell biologist at Duke University in Durham, North Carolina. Guided by a specific time frame, scientists may find it easier to identify factors that allow the heart to heal, he says.

The authors speculate that, in the first week of life, a genetic program instructs the heart cells to stop dividing, but the loss of regeneration could also be affected by the disappearance of hormones or other environmental signals that trigger cell division during this time. The authors are now looking for genes, gene silencers and drugs that could extend the regenerative period and reawaken it in the adult heart, says Eric Olson, a co-author and molecular biologist at the University of Texas Southwestern Medical Center.

The results could be bad news for attempts to use stem cells to regenerate the heart, says Mark Keating, a cardiologist at the Novartis Institutes for BioMedical Research in Cambridge, Massachusetts. "This work doesn't prove that those efforts won't be successful, but it doesn't make it more encouraging, either," he says. 

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