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Secret of Heart Regeneration Uncovered




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Newts can regrow a limb. Some lizards can sprout new tails. Even humans can replace some damaged tissue in organs, such as the liver. But none can accomplish what the zebra fish, a common denizen of home aquariums, can do: regenerate their hearts. Biologists have long known about the zebra fish's cardiac ability, and now researchers think they have unlocked the secret of the process, which may provide essential clues for human heart repair.

Kenneth Poss and his colleagues at Duke University found that zebra fish, Danio rerio, regenerate heart muscle in two synchronized steps. Within five days of removing about 20 percent of an adult zebra fish heart ventricle, undifferentiated progenitor cells begin to line the injured area and turn into cardiac muscle cells, which grow and divide, building new heart muscle. Meanwhile, developmental genes in the epicardium--a cell layer that surrounds the entire heart and influences embryonic heart development--switch on, activating the epicardial cells. Most of these cells form a new layer to cover the wound and the regenerating heart muscle, but some also create blood vessels for the growing muscle, "fulfilling the same role as they do when the embryonic heart develops," Poss says.

A growth factor signal orchestrates the two processes so that they converge to mend the zebra fish heart, according to the study that appears in the November 3 issue of Cell. This chemical, produced by the heart muscle cells, activates receptors on the surface of the epicardial cells, signaling it to form a new heart lining. If the communication between the two cell types is blocked, the zebra fish heart starts to scar and cannot completely regenerate.

Like zebra fish, mammal hearts have progenitor cells and an epicardium, but the formers "found a way to regenerate effectively," Poss says. The regenerative mechanism discovered in this fish could "give people who are eager to repair human hearts a pathway to hone in on," says Deborah Yelon, a researcher at New York University who studies zebra fish but was not involved in the study. The current findings suggest strategies that can be tested in human hearts, such as introducing growth factors and activating the receptors on epicardial cells, she says. "Maybe we can get mammalian progenitor cells to behave more like zebra fish cells," she adds. The study also highlights the role of the epicardium, a cell layer that is studied extensively in zebra fish embryonic development but receives little attention in adults. Poss hopes that researchers will also "take a closer look at the epicardium in injured mammalian hearts and to potentially look at whether epicardial cells can be used therapeutically."

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