Zebrafish used in research at the University of Utah. Credit: Brian Maffly, University of Utah
Key points:
- Zebrafish can regenerate their hearts after injury, while other fish species like medaka cannot.
- Researchers injured fish hearts to mimic a human heart attack and found species differences in immune cells, cell signaling and alterations in the structure of the heart.
- The team hopes their study can inform future research into regeneration and eventually advance medical treatments.
While a heart attack leaves a permanent scar on a human heart, other animals—some fish and amphibians—can clear cardiac scar tissue and regrow damaged muscle. In a new study, published in Biology Open, researchers investigate the molecular and cellular mechanisms underlying cardiac regeneration in the hopes of advancing medical treatments.
Researchers compared two fish species—zebrafish and medaka. Zebrafish can regenerate their hearts, but medaka cannot. They used a cryoprobe to injure the fish hearts in a manner similar to a human heart attack. After three days or fourteen days, the team extracted the fish hearts and dissolved them into a single-cell solution that allowed for RNA sequencing. The team used sequencing to identify markers indicating how fish respond to the injury.
The team characterized differences in immune cell recruitment and behavior, epicardial and endothelial cell signaling, and alterations in the structure and makeup of the heart. They determined that medaka lacked a certain type of muscle cell that was present in zebrafish and that the species differed in their immune responses.
“Zebrafish have this immune response that is typical of what you might see during a viral infection, called an interferon response,” said lead author Clayton Carey of University of Utah. “That response is completely absent in medaka.”
After the cardiac injury, zebrafish formed a transient scar that did not calcify into rigid tissue. Over time, new muscle replaced the damage cardiac tissue to heal the heart. While the team was able to characterize this regeneration and link it to the immune system response, they need to perform more research to understand exactly how the process occurs.
“The more we learn about how animals can regenerate tissues, that’s going to help us think about our limitations and how we might engineer strategies to help overcome those,” explained senior author Jamie Gagnon, professor at University of Utah. “Our hope is that we use this knowledge to generate more focused experiments in mammals, and then maybe someday in human patients.”