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Zebrafish Study with Human Heart Implications

Zebra Fish

Researchers led by Salk professor Juan Carlos Izpisúa Belmonte have identified a population of heart cells in zebrafish with the amazing ability to regenerate within a month after 20 percent of the tissue has been destroyed. The finding, published in Nature, could provide insight into how mammalian hearts might be coaxed into repairing themselves after injury brought on by heart attack.

Interestingly, it is not stem cells that repair the injured fish hearts. Instead, the patch-up work is done by differentiated cardiac muscle cells known as cardiomyocytes, the cells whose normal job is to supply the contractile force of the heart.

"What the results of our study show is that mother nature utilizes other ways besides going all the way back to pluripotent stem cells to Zebrafish Study with Human Heart Implications regenerate tissues and organs," says Izpisúa Belmonte, noting that, at least in fish, the body may have evolved surprising repair strategies driven by cell types more seasoned than stem cells.

Human hearts cannot undergo these types of regenerative changes on their own. When damaged by heart attack, our heart muscle is replaced by scar tissue incapable of contracting. However, prior to heart failure, damaged mammalian heart muscle cells enter a save yourself state known as "hibernation," in which they cease contracting in an effort to survive.

Chris Jopling, a postdoctoral fellow of Izpisúa Belmonte's at the Center for Regenerative Medicine in Barcelona who worked with researchers at the Salk, sees human heart "hibernation" as significant. "During heart regeneration in the zebrafish, we found that cardiomyocytes displayed structural changes similar to those observed in hibernating cardiomyocytes," he said, noting that those changes were actually necessary before the fish cardiomyoctes could start dividing. "Because of these similarities, we hypothesize that hibernating mammalian cardiomyocytes may represent cells that are attempting to proliferate."

So the good news is that mammalian hearts can undergo a kind of metabolic "downsizing" that is a prelude to cell division. "This idea fits nicely with the findings from a number of groups — that forced expression of cell cycle regulators can induce cardiomyocyte proliferation in mammals," says Jopling. "Maybe all they need is a bit of a push in the right direction."