Injured baby hearts may be coaxed to regenerate

Shots of a growth factor protein reduce cell death in mice

An injectable protein might rejuvenate cell growth in infants’ hearts after cardiac surgery. Experiments on mice and on heart cells obtained from infants born with congenital heart disease suggest that neuregulin 1, a human growth factor, can put infant heart cells on a path that mimics normal growth rather than stalling out. The report appears April 1 in Science Translational Medicine.

Neuregulin 1 is already being tested in adults to boost recovery from heart failure, but it hasn’t been tried in infants with heart disease, says study coauthor Bernhard Kühn, a pediatric cardiologist at the University of Pittsburgh and Children’s Hospital of Pittsburgh. The need is there, he says. About 1 in 100 newborns are born with minor congenital heart defects, and about 1 in 1,000 babies have heart issues severe enough to need surgery. These defects, such as a hole in the heart or defective valve, benefit greatly from surgery, Kühn says. But many heart cells die in the repair process, and scar tissue can limit the heart’s pumping capacity.

What’s more, heart muscle doesn’t regenerate as readily as skin or liver does. The new tests in mice and in human tissues show that adding neuregulin 1 reduces cell death and orchestrates regeneration of heart muscle cells. “I don’t think this will replace surgery,” Kühn says, “but our therapy can support the surgical approach.”

The researchers scarred the hearts of infant mice with a two-second touch of a probe cooled with liquid nitrogen. The cold damaged the outside of the heart, and mice left untreated lost heart function within two weeks. But mice that received daily injections of neuregulin 1 starting promptly after scarring rebuilt their supplies of heart muscle cells “to near-normal levels” over a month, Kühn says. Heart pumping capacity improved as well. Mice that received neuregulin 1 injections starting four days after the scarring fared worse, suggesting that there is a small window of time in which the animals — and possibly human babies — are able to regenerate heart muscle and take advantage of a boost from neuregulin 1.

The researchers also obtained human heart tissue from children with congenital heart disease who had undergone surgery. In lab dishes, these tissues didn’t grow as well as tissue from the hearts of healthy kids. When Kühn’s team treated postsurgical tissues with neuregulin 1, tissue from heart patients who were less than 6 months old responded well. These tissues showed substantially less cell death and more cell division than did tissues from heart patients older than 6 months.

The new study bolsters an understanding that as humans age, they have a dwindling supply of heart cells that can regenerate and repair tissues, says Hesham Sadek, a cardiologist at University of Texas Southwestern Medical Center in Dallas. Neuregulin 1 seems to enhance proliferation in those cells that haven’t yet lost that capacity. As such, he says, “it’s an important tool.”

Ultimately, Sadek envisions neuregulin 1 and possibly other growth enhancers getting tested in neonatal heart surgery trials. “But surgeons will have to come on board with that,” he says. Currently, surgeons operate on hearts with little expectation of heart cell proliferation, he says.  Kühn says one scenario would have infants recovering from heart surgery randomly assigned to get the best standard care or that plus neuregulin 1.

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