However, Poss and colleagues found that the process more closely resembles what happens when a salamander regenerates a lost limb. In the salamander, the site of injury becomes the gathering point for a mass of undifferentiated stem, or progenitor, cells, which are immature cells with the potential to be transformed into other cell types. This mass of undifferentiated cells is known as a blastema. As the progenitor cells receive the correct biochemical cue, they turn into distinct cell types, such as bone, muscle and cartilage, to form the new limb.
Poss believes that when a portion of the heart tissue is removed from zebrafish, a blastema forms at the site of injury. However, the progenitor cells will not achieve their full regenerative potential without interactions with the layer of "epicardial" cells that forms over the blastema. The entire heart is wrapped in a membrane known as the epicardium.
By the third day after injury, the epicardial cells begin to cover the injury site, a process that takes approximately two weeks. The precursor cells within the blastema begin to differentiate into cardiac muscle cells and proliferate within the first three to four days after injury, the researchers found in their experiments.
"Within days of the injury, we find a significant increase in the expression of certain genes in the epicardial cover," Poss said. "These genes are typically expressed only during embryonic development of the cardiovascular system. The epicardial cells mobilize to cover the wound and blastema, and help provide new blood vessels, creating a protective niche where the new heart muscle can grow."
The researchers found that biochemical signaling between the blastema and the epicardium is controlled in part by proteins called fibroblast growth factors, which are involved in wound healing and embryonic development.'"/>