Zebrafish study may shed light on cell regeneration in human heart

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London, March 25 (ANI): A new Spanish study has found that cardiac muscle cells known as cardiomyocytes carry out repair in an injured zebrafish heart - a finding that could provide insight into how human hearts could be made to repair themselves after a heart attack.

The research, conducted by Juan Carlos Izpisza Belmonte and his colleagues at the Salk Institute for Biological Studies and the Center of Regenerative Medicine in Barcelona (CMRB), found that these cellular grown-ups outperform stem cells in cardiac repair.

Izpisza Belmonte, professor in the Gene Expression Laboratory, said: "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 regenerate tissues and organs."

Izpisza Belmonte also noted, that at least in fish, the body may have evolved surprising repair strategies driven by cell types more seasoned than stem cells.

To identify which cells actually filled in excised zebrafish heart muscle, the researchers first used some genetic engineering to only make cardiomyocytes "transgenic" by inserting into them a tracer gene that made them glow green under a microscope.

Thereafter, they chopped off about 20 per cent of each fish ventricle and waited a couple of weeks for the hearts to regenerate: if regenerated heart muscle didn't glow, it would mean that cells other than cardiomyocytes, such as a cardiac stem cell population, had replaced the damaged muscle.

However, all regenerated heart muscle cells glowed green, indicating that well established cardiomyocytes remaining after injury had likely regressed to a more "youthful" state, started dividing again to replenish lost cells, and then matured a second time into new heart muscle.

The team also demonstrated that cardiomyocytes recaptured lost youth in part by re-activating the production of proteins associated with cell proliferation, factors typically expressed in immature progenitors.

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 Izpisza Belmonte's at CMRB and first author of the study, believes human heart "hibernation" is significant.

He said: "During heart regeneration in the zebrafish we found that cardiomyocytes displayed structural changes similar to those observed in hibernating cardiomyocytes.

"Because of these similarities, we hypothesize that hibernating mammalian cardiomyocytes may represent cells that are attempting to proliferate."

Thus, it can be said that mammalian hearts can undergo a kind of metabolic "downsizing" that is a prelude to cell division.

Jopling said: "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.

"Maybe all they need is a bit of a push in the right direction."

Izpisza Belmonte added: "We can no longer view differentiated cells as being a static endpoint of the differentiation process.

"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."

The study has appeared in the March 25, 2010 issue of Nature. (ANI)

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