The Heart That Heals Itself? A New Study Shows Adult Human Cells Can Divide Again

Leon Wirz
Dec 1
5 min read

Based on a study published in npj Regenerative Medicine (2025), Icahn School of Medicine

Introduction

For decades, cardiology has lived with a frustrating truth: once damaged, the human heart cannot properly repair itself. After a heart attack, millions of cardiomyocytes die, and instead of regenerating, the tissue scars over. This lack of natural regeneration is one of the main reasons why heart failure remains so common and so expensive for healthcare systems, including Switzerland’s, where cardiovascular conditions consume billions of francs each year.

A new study challenges this long-held belief. Researchers at the Icahn School of Medicine at Mount Sinai report that adult human cardiomyocytes (even from people in their 40s and 50s) can be induced to divide again. The key lies in reactivating a gene called Cyclin A2 (CCNA2), which normally switches off after birth.

If these findings translate into clinical practice, the implications for medicine, insurers, and patients could be profound.

The Core Discovery

The central finding of the study is simple but groundbreaking: by reintroducing Cyclin A2 into adult human cardiomyocytes, the cells re-enter the cell cycle and undergo complete cytokinesis (meaning they divide into two fully formed daughter cells).

This is not partial activity or incomplete DNA replication. It is the real thing: Actual division of mature human heart muscle cells, captured live on camera.

Even more importantly, these daughter cells maintain essential features of healthy cardiomyocytes, including intact sarcomere structures and proper calcium handling. This suggests that the divided cells are not only alive, they may be functionally useful.

How the Study Was Conducted

To ensure precise and safe delivery of CCNA2, the researchers engineered a cardiac-specific adenoviral vector using the cardiac troponin T (cTnT) promoter. This guarantees gene activation only in cardiomyocytes, reducing the risk of affecting other tissues. (The vector design is illustrated on page 3.)

The team obtained human cardiomyocytes from donors aged 21, 41, and 55. These cells were kept alive in culture, transduced with the CCNA2-carrying vector, and monitored over several days. Time-lapse fluorescence microscopy provided direct evidence of cell division, particularly in the 41- and 55-year-old samples. (Images on pages 3–4 show cytokinesis in action.)

Once division occurred, the researchers tested whether the daughter cells behaved like cardiomyocytes. They embedded them in 3D matrix culture and recorded calcium flux, a hallmark of proper electrical activity. The CCNA2-induced daughter cells passed this functional test. (Figure on page 4 shows the calcium flux patterns.)

To understand what was happening at the molecular level, the team performed deep sequencing on both human and mouse samples. This included bulk RNA sequencing of fetal and adult human hearts and single-nucleus RNA sequencing (snRNA-seq) of mouse hearts. The sequencing revealed a clear shift toward a more fetal-like, regenerative transcriptional program, but without full dedifferentiation. In other words, the cells briefly become more flexible, just enough to divide, while preserving their identity. (Relevant maps and heatmaps appear on pages 5–7.)

Key Findings

The most striking result is that adult human cardiomyocytes can regain the ability to divide, even decades after this capability is normally shut down. This contradicts the long-standing assumption that heart muscle cells become permanently post-mitotic after early childhood.

A second major finding is that Cyclin A2 does not simply force the cells into uncontrolled proliferation. Instead, the gene induces a controlled, developmentally relevant reactivation of cell-cycle pathways. Single-cell analysis identified a specific subpopulation of cardiomyocytes (referred to as Pro-vCM10) that responds particularly strongly to CCNA2. These cells express high levels of mitotic regulators such as Mki67, Aurkb, Anln, and Kif23, as well as classic reprogramming and developmental factors like Gata4 and Sox2. (See pages 6–8.)

Equally important is what does not happen: Cyclin A2 does not trigger pathological hypertrophy or fibrosis pathways. When the authors compared CCNA2-induced transcriptional changes to those seen in hearts under pressure overload (a model of disease), the differences were clear. Hypertrophic hearts activate stress responses and fibrosis. CCNA2 hearts activate cytokinesis and regeneration.

This distinction is crucial because it suggests that Cyclin A2 is working with the heart’s biology, not against it.

Limitations of the Study

Despite its promise, several limitations must be addressed. The experiments were carried out in vitro, meaning outside the body, and cultured cardiomyocytes do not perfectly replicate the complex environment of a beating heart. Fresh human cardiomyocytes are also fragile and may behave differently under culture stress.

Adenoviral vectors, although widely used in research, can trigger immune responses in patients. More refined delivery systems (such as adeno-associated viruses (AAV), lipid nanoparticles, or mRNA approaches) will likely be needed for clinical application.

Finally, this study demonstrates feasibility, not therapeutic effect. Showing that cardiomyocytes can divide is an important first step, but repairing an injured heart in vivo will require proving that these cells integrate, survive long-term, and improve cardiac function.

Relevance for Switzerland

Switzerland’s healthcare system already faces rising economic pressure from chronic cardiovascular diseases. Heart failure alone leads to frequent hospitalizations, long rehabilitation, productivity loss, and costly long-term medical therapy under KVG/LAMal.

A successful gene therapy that regenerates heart tissue could dramatically reshape the cost structure:

fewer lifetime hospital admissions for heart failure,
reduced need for device therapy and transplantation,
less chronic medication use,
improved long-term patient independence.

For insurers, the shift would be significant: high upfront treatment costs, but lower long-term expenditure. For Swiss biotech, this research aligns with the country’s growing focus on regenerative medicine, gene therapy, and precision delivery technologies, offering substantial innovation potential.

Potential Impacts of a Successful Therapy

A therapy based on CCNA2 would represent a new era in cardiology. Instead of managing symptoms, clinicians could aim to restore damaged myocardium. Patients might regain heart function after myocardial infarction, potentially avoiding years of deterioration. Healthcare systems could see a shift away from chronic treatment toward regenerative interventions that are administered once but offer lasting benefit.

Such an approach could also reduce the pressure on transplantation programs, which face donor shortages and high postoperative costs. Regenerative treatments would not replace transplants entirely, but they could meaningfully reduce demand.

Risks

Gene therapies that manipulate the cell cycle always carry theoretical risks. Uncontrolled proliferation must be avoided at all costs, and even a small number of off-target effects could have serious consequences. Immune reactions to the viral vector and potential arrhythmias due to immature cardiomyocytes also require careful evaluation.

These risks do not invalidate the approach but emphasize the need for rigorous preclinical and clinical testing.

Overall Assessment

This study represents one of the most compelling advances in cardiac regeneration to date. It offers direct visual and molecular evidence that adult human cardiomyocytes are not irreversibly locked out of the cell cycle. Through targeted reactivation of Cyclin A2, the cells can divide again cleanly, safely, and while retaining key cardiac functions.

The findings are foundational rather than immediately clinical, but they redefine what is biologically possible. For the field of regenerative medicine, this is a milestone. For healthcare systems like Switzerland’s, it foreshadows a future where treating the heart means rebuilding it.

What Comes Next

Future research will need to answer several pressing questions: How can CCNA2 be delivered safely into the human heart? Which patient groups would benefit most? Can the proliferating cardiomyocytes integrate and contribute to long-term cardiac function?

Developing precision gene delivery, identifying the most responsive cardiomyocyte subpopulations, and performing controlled in vivo studies will be crucial steps. If these succeed, clinical trials may follow, potentially within the next decade.

Reference

Bouhamida, E., Vadakke-Madathil, S., Mathiyalagan, P. et al. Cyclin A2 induces cytokinesis in human adult cardiomyocytes and drives reprogramming in mice. npj Regen Med 10, 47 (2025). Link