Newborn mice can fix their broken hearts

Day-old mice can regenerate their hearts after a slice through the apex. Scientists are looking for genes and drugs that can extend the regenerative period in adults.

For a few fleeting days, the beating heart inside newborn mice can regenerate itself after an injury. Stem cells, surprisingly, were not involved.

Scientists can now find ways to harvest this self-regeneration for adult human hearts, “an important step in our search for a cure for heart disease, the No. 1 killer in the developed world,” says study author Hesham Sadek.

Certain fish, frogs, newts, and even mammal embryos can rebuild their heart muscle after injuries, but this has never really been found in adult mammals. Zebrafish (Danio rerio) can recover lost cardiac tissue throughout their life, even after a 20% amputation.

Although adult mammals can replace some damaged heart muscle cells, the turnover rate in humans is lower than 1% a year – not enough to revitalize the organ after a heart attack or other major injury that causes scar formation [Nature].

Scientists don’t know whether that’s because we’re missing the capacity for cardiac regeneration altogether or whether we do have the capability, but it got switched off right after birth.

So to see what that’s all about, researchers from the University of Texas Southwestern Medical Center surgically removed part of the heart (pictured) in 1-day-old mice – as much as 15% of the muscle tissue in the walls of the left ventricle (one of the lower chambers of the heart).

Afterwards, the remaining heart muscle cells – called cardiomyocytes – proliferated, triggering the regrowth of a functioning, anatomically normal ventricle.

They fully recovered muscle tissue within 3 weeks of the operation, and their left ventricle pumped blood normally within 2 months.

This ability is, however, lost by the time the mice turned 7 days old – as the team saw when they tried the procedure in week-old mice. “By seven days this remarkable regenerative is lost and instead of regrowing that tissue back, there is heart failure,” Sadek says. “In humans, it may be a few months after birth that this is lost.”

Study author Enzo Porrello adds: "There is some evidence that the newborn human heart does not scar following injury, suggesting that it might also be capable of regenerating during early life."

At first, the researchers thought that stem cells were involved, because they do mobilize after injuries. But turns out, all the new heart muscle cells came from preexisting cells rather than stem cells.

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. Now they’re looking for genes, drugs, or growth factors to extend the regenerative period and reawaken the mechanism in the adult heart, says coauthor Eric Olson.

“We’re looking at a few genes that could regulate this process, and then we can look for drugs that activate the genes,” Sadek says. “Maybe we can remind the heart how to do this.”

The findings were published in Science last week.

Image: Science/AAAS

This post was originally published on Smartplanet.com

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