Scientists from the Bakkers group at the Hubrecht Institute have made a groundbreaking discovery, using a zebrafish-derived protein to repair damaged mouse hearts. The study, published in Nature Cardiovascular Research, demonstrates that the protein Hmga1 activates dormant repair genes in mice, restoring heart function without adverse side effects like heart enlargement.
Unlocking Heart Regeneration
Following a heart attack, human hearts lose the ability to regrow muscle cells, often leading to heart failure. Zebrafish, however, can fully regenerate their hearts within 60 days of injury.
“We aimed to uncover why some species, like zebrafish, can regenerate their hearts while others, like humans, cannot,” said Professor Jeroen Bakkers, the study’s lead author.
Researchers identified Hmga1 as a key protein in zebrafish heart repair. Active during embryonic development, Hmga1 typically remains dormant in adult mammals. However, when applied to damaged mouse hearts, it triggered cell division and repair, significantly improving heart function. Importantly, these effects were localized to the damaged area, with no unwanted growth in healthy tissue.
Clearing Molecular ‘Roadblocks’
The study revealed that Hmga1 facilitates repair by unpacking chromatin—a structure that packages DNA—allowing dormant genes to activate. This process enables damaged heart cells to begin dividing and growing again.
From Zebrafish to Humans
While Hmga1 is inactive in adult human hearts, it is present during embryonic development, suggesting the potential for gene therapies to restore regenerative capabilities.
“These findings lay the groundwork for targeted therapies to unlock heart regeneration in humans,” said Bakkers.
Next Steps
Further research will test the protein’s effects on human heart cells in collaboration with UMC Utrecht. The findings are part of the Netherlands’ OUTREACH consortium, involving researchers from several institutions.
“This collaboration allowed us to translate zebrafish discoveries to mammals and, ultimately, humans,” said co-first author Mara Bouwman.
As reported by medicalxpress, the study marks a significant step toward regenerative treatments aimed at preventing heart failure, with ongoing efforts under the Summit program DRIVE-RM to refine and expand these findings.