Self-healing hearts
How zebrafish regenerate heart muscle cells
zebrafish can completely replace damaged heart muscle cells: The affected organ becomes fully functional again. How do they manage this? Researchers at the University of Ulm have discovered that a specific cell-to-cell communication signal helps them to cope better with replication stress. This stress occurs during cell division and inhibits tissue regeneration in humans and mammals as they age. In zebrafish, on the other hand, a signaling protein ensures that the cells of the damaged organ continue to divide and thus multiply. The results were published in the journal Nature Communications.
Zebrafish
Elvira Eberhardt
In humans, a heart attack often leads to permanent damage because the affected tissue does not regenerate sufficiently. Zebrafish, on the other hand, can compensate for injuries to the heart that cover up to a third of the organ. "A sufficiently successful division activity of the heart muscle cells is crucial for the successful regeneration of injured tissue," explains Professor Gilbert Weidinger from the Institute of Biochemistry and Molecular Biology (iBMB) at the University of Ulm. The scientist coordinated a study that revealed why zebrafish are so much better at repairing tissue damage to the heart than humans. The research team discovered that a special cell-to-cell communication signal is crucial. This so-called BMP signaling protein helps zebrafish to deal with replication stress.
Replication stress hinders cell division in humans, but not in zebrafish
When DNA is replicated during cell division, the cell can come under replication stress: DNA lesions, strand breaks or even a lack of nucleotides - the building blocks of DNA - lead to a slowdown or even a halt in replication. The cells can no longer divide and multiply sufficiently and the tissue no longer regenerates. "Our research results have shown that zebrafish cells are also exposed to this stress during the repair of tissue damage, but are much better able to cope with it," explains Weidinger. The BMP signaling protein helps them to do this. The abbreviation BMP stands for "Bone Morphogenetic Protein". BMPs are part of a signaling system that plays a key role in embryonic development and organ development. These signaling molecules, which act locally on surrounding cells, help zebrafish cells to exploit their full regenerative potential. "Even with injuries that affect up to a third of the heart muscle cells, zebrafish are able to restore the original number of cardiomyocytes within 30 days," says Denise Posadas Pena. The PhD student at the iBMB co-authored the study published in Nature Communications.
The research team also succeeded in significantly improving the regenerative capacity of human cells experimentally. The scientists tested this on hematopoietic stem and progenitor cells (HSPCs) and skin cells. When these cells are placed under replication stress in culture, BMP signals can protect them from this. "The research results may help to develop new therapeutic approaches for better tissue regeneration. So that injured tissue can heal itself better," believes Gilbert Weidinger.
"Our results show that regenerating zebrafish hearts can serve as a model for anti-ageing processes. It helps us to identify factors that could alleviate or even reverse ageing processes," says stem cell expert Professor Hartmut Geiger. The head of the Ulm Institute of Molecular Medicine was also involved in the study. Scientists from Ulm, Bonn, Heidelberg, Bologna, Oxford and Zurich were involved in the research project. The study was funded as part of the Ulm Collaborative Research Center SFB 1506 "Aging at Interfaces".
Note: This article has been translated using a computer system without human intervention. LUMITOS offers these automatic translations to present a wider range of current news. Since this article has been translated with automatic translation, it is possible that it contains errors in vocabulary, syntax or grammar. The original article in German can be found here.
Original publication
Mohankrishna Dalvoy Vasudevarao, Denise Posadas Pena, Michaela Ihle, Chiara Bongiovanni, Pallab Maity, Dominik Geissler, Hossein Falah Mohammadi, Melanie Rall-Scharpf, Julian Niemann, Mathilda T. M. Mommersteeg, Simone Redaelli, Kathrin Happ, et al. "BMP signaling promotes zebrafish heart regeneration via alleviation of replication stress"; Nature Communications, Volume 16, 2025-2-17
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