Zebrafish Protein Hmga1 Sparks Hope for Human Heart Regeneration
Have you heard of the Zebrafish? Scientists from the Hubrecht Institute have made has now recently discovered new findings in heart regeneration. Lanza’s team was also able to fix a broken mouse hearts using a protein from zebrafish called Hmga1. Famed for the peculiar characteristic of the ability to regenerate the heart muscle, the zebrafish serves as the model for unusual approaches to heart failure in people. The findings, published in the journal Nature Cardiovascular Research, could be used in translating such concepts into regenerative treatments for people.
Heart failure is usually the result of heart attacks during which millions of cardiac muscle cells cannot be replaced. While the human heart has limitations to regeneration, zebrafish hearts can regenerate completely in two months after the injury. The team, headed by Dr Jeroen Bakkers, wanted to know why a zebrafish has such superb regenerative capacity when mammals, including us, do not. So now, knowing and using Hmga1, they have found a valuable possibility that could change the entire face of heart therapy.
To achieve that, the research included comparing the genes of zebrafish and mouse heart tissues when regeneration was in process. One was for the gene coding for the Hmga1 protein, which was active in the zebrafish, whereas it remained inactive in the adult mouse. Hmga1 protein is essential for cell growth in embryonic development but is nonfunctional in the adult hearts. However, the team was able to prove that when this protein is reactivated in mice, it does demonstrate a highly effective regenerative ability.
Hmga1 operates like a road grader and flattens “roadblocks” on chromatin – the protein and DNA scaffold for the nucleus. These barriers maintain the repression of the above genes in the adult cell.” It could be said that the protein helps the complex loosen the chromatin and get the repair genes activated again. Hmga1 substantially enhanced cell division and growth in damaged mouse hearts when administered similarly only in the affected areas, constituting improved heart function without negative side effects such as uncontrolled growth or heart enlargement.
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According to the researchers, the very damage transmits signals that specify the regions into which Hmga1 activity is to be directed. Such specificity reduces side effects and demonstrates the protein’s benefits. The study also reveals the fact that the Hmga1 gene is not expressed in adult human hearts, but exists and is active during embryonic development. This led to the potential of designing gene therapies that can provoke the heart to start regenerating in person.
The work is truly multidisciplinary, assembling zebrafish and mammalian stem cell researchers. This work was performed in the context of the OUTREACH consortium supported by the Dutch Heart Foundation and Hartekind Foundation, with participation of the Van Rooij and Christoffels Laboratories, Amsterdam UMC. This way, various public-private collaborations made it easy to translate findings from zebrafish to mice with the end product being human hearts.
This is important even though researchers have come a long way towards achieving workable clinical applications that describe complex systems. Further plans are to perform experiments on human cardiomyocytes in cell culture, which will be investigated collaboratively with institutions such as UMC Utrecht. Also, in 2025, the DRIVE-RM Summit program is planned to be launched to progress the development of heart regeneration therapies.
This finding provides fresh hope to create specific, non-harmful therapies for heart failure. If researchers can stimulate the heart’s stem cells and discover how to repair damaged tissue, elective operations such as transplants may become outdated as they invent a literally heart felt cure for the millions of sufferers across the globe.