Around the globe, heart disease remains one of the top causes of death. Once patients begin to suffer from serious heart problems, like heart attacks and heart failure, the heart muscles become damaged and are difficult to treat and repair. Although many therapies have been developed to treat symptoms, full recovery to a pre-disease state has been essentially impossible. This is due to a lack of regeneration ability in adult human heart cells. Studies using stem cells or progenitor cells for repair have demonstrated limited efficacy in clinical trials, thus far.
However, there may be new hope for these patients. Researchers from the Icahn School of Medicine at Mount Sinai in New York have been working to turn back time by switching on a gene known to regenerate heart muscle cells, or cardiomyocytes. Their study, recently published in npj Regenerative Medicine, indicates that adult human hearts may be given the ability to regenerate themselves with future therapies.
CCNA2—the ‘master regulator’ of the heart cell cycle
The study focuses on a gene called Cyclin A2 (CCNA2), which is functional during fetal growth and shuts off shortly after birth, limiting the ability for cell regeneration. In fetuses, while CCNA2 is still functional, it plays an important role in cell division and growth, facilitating the creation of new heart cells. However, adults appear to still have a very limited capacity for repair.
“There has been evidence of low-level cardiomyocyte turnover in the healthy human heart, but it is very limited, and this ability declines with age. Thus, cardiac regeneration in response to injury such as myocardial infarction (MI) remains a clinical challenge,” the researchers write.
The study authors refer to CCNA2 as the “master regulator” of the heart cell cycle. So far, studies surrounding CCNA2—mostly in animal models—have shown promise in its ability to be switched back on.
A string of promising results
In 2014, one of the lead authors, Hina Chaudry, was involved in another study in which CCNA2 was activated in a pig that had recently suffered from a heart attack. CCNA2 successfully induced heart cell division in the pig and its heart function improved. Studies involving mice showed similar results.
In the new study, the team moved on to testing out this method on in vitro human cells from adults aged 41 and 55 years old. To do this, they engineered a harmless virus, capable of expressing human CCNA2 and delivered it to the cultured cells. They then performed live-cell imaging to track cell division and structure. Finally, they performed RNA sequencing in mouse and human heart samples to analyze any changes in gene expression.
The results were promising—CCNA2 induced heart cell regeneration in the 41 and 55-year-old heart cells, reactivating the fetal-like and regenerative gene programs in the cells. They found that the resulting daughter cells retained heart muscle structure and function, and continued to handle calcium effectively.
Additionally, RNA sequencing in mice revealed a subpopulation of heart cells with active cell division and reprogramming gene signatures, even after CCNA2 expression.
“Taken together, these findings suggest that the partial reprogramming induced by CCNA2 reflects a controlled activation of developmental programs, consistent with regenerative responses observed in neonatal hearts, and aligns with prior evidence that modest increases in cell cycle gene expression can enhance cardiac regeneration capacity,” the study authors write.
A new hope for future heart disease patients
While further research is needed to optimize the delivery of CCNA2 and conduct human trials, this research presents an exciting opportunity for future therapies with the ability to repair hearts instead of only treating symptoms. Potential applications include regenerative gene therapy to repair damage after heart attacks, or even alternatives to heart transplantation and current cell therapies.
“Unlike cell transplantation or non-specific mitogens, CCNA2 integrates proliferative drive with lineage fidelity, thereby offering a safer and more effective strategy for cardiac regeneration. Future work defining the molecular signatures of proliferative CCNA2-positive cardiomyocytes will enable the development of precision-guided therapies, whether through direct gene transfer or by reactivating endogenous CCNA2 using antisense approaches,” the study authors write. https://medicalxpress.com/news/2025-11-reactivating-fetal-gene-enables-adult.html
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