Chris Jopling, Ph.D., a postdoctoral fellow of Izpis a Belmonte's at CMRB and first author of the study, 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."

A search is on for factors that could supply that "push." Although he is optimistic about the outcome, Izpis a Belmonte also feels that the study should caution researchers not to overlook potential contributions that mature cells might make to regeneration. "We can no longer view differentiated cells as being a static endpoint of the differentiation process," says Izpis a Belmonte, who also directs the CMRB. "If we could mimic in mammalian cells what happens in zebrafish, perhaps we could be in a position to understand why regeneration does not occur in humans."

Also contributing to this work were Merce Marti, Ph.D., Angel Raya, M.D., Ph.D., Edward Sleep, and Marina Raya, all of the CMRB in Spain.

The study was funded in part by Fundacion Cellex, the Ipsen Foundation, the G. Harold and Leila Y. Mathers Charitable Foundation, the National Institutes of Health, and Sanofi-Aventis.

Source: The Salk Institute for Biological Studies