For some years now researchers have been investigating the biochemistry of species such as salamanders and zebrafish that are capable of regrowing limbs and internal organs. It is as yet unknown how hard it will be to improve human regenerative capacity using what is learned from this research, but definitive answers may emerge over the next decade:
While the human heart can't heal itself, the zebrafish heart can easily replace cells lost by damage or disease. Now, researchers have discovered properties of a mysterious outer layer of the heart known as the epicardium that could help explain the fish's remarkable ability to regrow cardiac tissue. After an injury, the cells in the zebrafish epicardium dive into action - generating new cells to cover the wound, secreting chemicals that prompt muscle cells to grow and divide, and supporting the production of blood vessels to carry oxygen to new tissues.
Researchers found that when this critical layer of the heart is damaged, the whole repair process is delayed as the epicardium undergoes a round of self-healing before tending to the rest of the heart. "The best way to understand how an organ regenerates is to deconstruct it. So for the heart, the muscle usually gets all the attention because it seems to do all the work. But we also need to look at the other components and study how they respond to injury. Clearly, there is something special about the epicardium in zebrafish that makes it possible for them to regenerate so easily. The epicardium is underappreciated, but we think it is important because similar tissues wrap up most of our organs and line our organ cavities. Some people think of it as a stem cell because it can make more of its own, and can contribute all different cell types and factors when there is an injury. The truth is we know surprisingly little about this single layer of cells or how it works. It is a mystery."
The new research showed that the process requires signaling through a protein called sonic hedgehog, and demonstrated that adding this molecule to the surface of the heart can drive the epicardial response to injury. Researchers also found that the epicardium produces a molecule called neuregulin1 that makes heart muscle cells divide in response to injury. When they artificially boosted levels of neuregulin1, even without injury, the heart started building more and more muscle cells. The finding further underscores the role of this tissue in heart health. The researchers now plan to perform larger screens for molecules that could enhance heart repair in zebrafish, and perhaps one day provide a new treatment for humans with heart conditions.