Heartbroken

The zebrafish (Danio rerio) belongs to the minnow family (Cyprinidae) and is an important model organism in scientific research, particularly in the areas of vertebrate development and gene function. More information can be found at the Zebrafish Information Network (ZFIN) which is an online database of housing genetic, genomic, developmental information, and data sets.

Did you know? Zebrafish have an incredible ability - you can chop of a chunk of their heart and they not only stay alive but they have only a few days of slow swimming before they once again appear completely normal. Crazy!

A paper published in the most recent issue of Nature contained a study in which researchers at the Salk Institute for Biological Studies and the Center of Regenerative Medicine in Barcelona (CMRB) identified the heart cell populations that allow the fish to have this amazing healing ability. My first thought was that it must be stem cell related. Not so. Rather it is cardiomyocytes a.k.a. muscle cells that contract the heart.

So how did they figure out that it was cardiomyocytes and not stem cells that accomplished the deed? First they inserted a tracer gene into all of the heart cells that made the cells glow green. Next they "injured" the heart by excising 20% of each ventricle (Basic Anatomy 101...those are the bottom chambers of the heart). Then they waited for a few weeks, waiting for the regeneration to complete, and then they took a look at the fish hearts again. Because only cardiomyocytes were made to glow green, if the whole heart was green then they were the ones to heal the injury, if not then something else was responsible.

The result: A glowing green fish heart. Neat.

How did the cells do it? The cardiomyocytes produced proteins associated with cell proliferation (factors you only see in immature progenitors). These proteins regressed the cells to a "youthfull" state, then they started dividing to fill in the missing area, and once again matured into new heart muscle.

They're fish, so why is this study important? Human heart muscle cannot regenerate after it is damaged (as with a heart attack), instead it produces un-contractable scar tissue. However, they do have the ability to enter a "hibernation" stage where they stop contracting in order to survive. This hibernation is similar to what the researchers saw in the regenerating zebrafish hearts. Forcing certain cell cycle regulators in mammalian cardiomyocytes to make these cells hibernate and regress could be the next direction to go in in heart regeneration research. What are these regulators? The search is on!

The Nature article is here: http://www.nature.com/nature/journal/v464/n7288/full/nature08899.html
and here's a write-up: http://www.sciencedaily.com/releases/2010/03/100324141957.htm

(image from www.mbl.edu)