In a groundbreaking discovery that could reshape the future of heart failure treatment, a team of international researchers has uncovered a new method to stimulate the regeneration of damaged heart tissue. The study, recently published in npj Regenerative Medicine, introduces an innovative strategy to promote cardiomyocyte proliferation—an advancement that offers renewed hope for patients suffering from ischemic heart failure, a condition that currently lacks curative therapies.
The research was led by scientists from the Michael E. DeBakey Department of Surgery at Baylor College of Medicine in Houston, Texas, in collaboration with the QIMR Berghofer Medical Research Institute in Brisbane, Australia, along with other international partners. Their collective findings present an exciting step toward enabling the heart to heal itself after injury.
Heart failure remains a global health challenge. In particular, ischemic heart failure, which results from the death of heart muscle cells (cardiomyocytes) due to reduced blood flow, is a leading cause of disability and death worldwide. When the heart experiences a heart attack, blood supply to certain areas is cut off, leading to permanent damage. Unlike many other organs, the human heart has a limited ability to regenerate the cardiomyocytes that are lost during such events. As a result, scar tissue forms in place of healthy muscle, causing the heart to progressively weaken and eventually fail.
The crux of this study lies in addressing one of the most stubborn limitations of cardiac biology—the inability of adult cardiomyocytes to re-enter the cell cycle and proliferate after injury. However, this new research offers a promising strategy to reverse that limitation by targeting the mechanisms that control calcium influx into heart cells.
“When the heart cannot replace injured cardiomyocytes with healthy ones, it becomes progressively weaker, a condition leading to heart failure,” explained Dr. Riham Abouleisa, co-corresponding author of the study and assistant professor in the Division of Cardiothoracic Surgery at Baylor College of Medicine. “In this study, we investigated a new way to stimulate cardiomyocyte proliferation to help the heart heal.”
Decades of research have shown that calcium ions are essential for cardiomyocyte contraction, but their role extends far beyond this fundamental function. Calcium signaling also regulates cellular processes such as growth, proliferation, and survival. However, in adult cardiomyocytes, calcium dynamics are tightly controlled to support contraction, and this regulation may limit their capacity to divide.
Previous studies hinted at a connection between calcium influx and the ability of cardiomyocytes to proliferate. Building on these observations, Dr. Abouleisa and her team hypothesized that reducing calcium entry into these cells could remove a key barrier to their division and regeneration. To test this theory, the researchers focused on a critical regulator of calcium influx—the L-Type Calcium Channel (LTCC).
LTCCs are responsible for allowing calcium ions to enter cardiomyocytes during each heartbeat. These channels play an essential role in maintaining the rhythmic contractions of the heart, but the new study suggests that they may also suppress the genes involved in cell proliferation. By pharmacologically and genetically inhibiting LTCCs, the research team discovered that they could enhance the expression of genes associated with cell cycle re-entry and proliferation in cardiomyocytes.
“We found that preventing calcium influx in cardiomyocytes enhances the expression of genes involved in cell proliferation,” Dr. Abouleisa said. “We prevented calcium influx by inhibiting L-Type Calcium Channel, a protein that regulates calcium in these cells. Our findings suggest that LTCC could be a target for developing new therapies to induce cardiomyocyte proliferation and regeneration.”
This pivotal discovery has significant implications for regenerative medicine. The research demonstrates that both pharmacological inhibitors and genetic approaches to block LTCC activity successfully induced cardiomyocyte replication. One of the key mechanisms identified in the study involves calcineurin, a calcium-sensitive enzyme that has long been known to influence cardiomyocyte biology. By modulating calcineurin activity through LTCC inhibition, the team was able to re-activate regenerative pathways that are normally dormant in adult heart cells.
The findings were validated across multiple experimental models, including human cardiac tissue slices cultured in the laboratory and live animal models of heart injury. These results provide compelling evidence that LTCC inhibition can stimulate cardiomyocyte proliferation in settings that closely mimic human disease.
“Abouleisa’s multi-continent collaborations led to a discovery that can revolutionize the use of current medicines that regulate calcium entry to the cells, such as Nifedipine, in heart failure patients,” commented Dr. Tamer Mohamed, co-author of the study and director of Baylor College of Medicine’s Laboratory for Cardiac Regeneration. Nifedipine and similar drugs, commonly used to treat high blood pressure and angina, are LTCC blockers. The new research opens the possibility that these existing medications—or next-generation versions designed specifically for regeneration—could be repurposed to promote cardiac repair.
The team’s work represents an important step toward the long-sought goal of regenerating human heart tissue after injury. “The premise of regenerating heart tissue, which once seemed like an impossible dream, is getting closer almost daily,” said Dr. Todd K. Rosengart, chair and professor of the Michael E. DeBakey Department of Surgery at Baylor College of Medicine. “The work of Dr. Abouleisa and the Baylor cardiac regeneration team represents a major step toward human trials that I believe are in the not-too-distant future.”
This groundbreaking research highlights the critical role of calcium signaling pathways in regulating cardiomyocyte proliferation and offers a potential therapeutic target for regenerative strategies in heart failure. Targeting LTCCs could enable clinicians to reawaken the heart’s dormant ability to regenerate, reducing the need for invasive interventions such as heart transplants or mechanical assist devices.
The potential applications of this discovery extend beyond ischemic heart failure. Many other forms of heart disease—whether caused by genetic defects, viral infections, or chronic stress—lead to the loss of cardiomyocytes and the accumulation of scar tissue. If therapies can be developed to stimulate the heart’s regenerative capacity, patients with a wide range of cardiac conditions could benefit.
Beyond the technical achievements of this research, it underscores the power of collaborative science. This project brought together experts in cardiothoracic surgery, regenerative medicine, molecular biology, and bioengineering from institutions on multiple continents. Their joint efforts demonstrate how team-based science can accelerate discoveries that have the potential to transform patient care.
Other contributors to the research include Lynn A. C. Devilée, Abou Bakr M. Salama, Jessica M. Miller, Janice D. Reid, Qinghui Ou, Nourhan M. Baraka, Kamal Abou Farraj, Madiha Jamal, Yibing Nong, Douglas Andres, Jonathan Satin, and James E. Hudson. Together, this group of scientists has opened an exciting new chapter in the field of cardiac regeneration.
Despite these promising results, challenges remain before this approach can be translated into therapies for patients. Researchers will need to carefully optimize the dosing and delivery of LTCC inhibitors to maximize regeneration without compromising the heart’s ability to contract effectively. Additionally, long-term studies are needed to ensure that stimulating cardiomyocyte proliferation does not increase the risk of arrhythmias or other adverse effects.
Nevertheless, the implications of this discovery are profound. It suggests that the key to healing the heart may lie in targeting pathways that have long been overlooked or misunderstood. With further research and clinical development, the ability to stimulate the heart’s own cells to regenerate could shift the paradigm of heart failure treatment from managing decline to restoring function and health.
The research team at Baylor College of Medicine and their international collaborators are now focused on moving these findings closer to clinical application. Human trials may not be far off, and the day when regenerative therapies for heart failure become a reality is inching closer. The heart, once thought to be beyond repair, may soon be able to heal itself—a possibility that offers hope to millions of patients worldwide.
More information: Lynn A. C. Devilée et al, Pharmacological or genetic inhibition of LTCC promotes cardiomyocyte proliferation through inhibition of calcineurin activity, npj Regenerative Medicine (2025). DOI: 10.1038/s41536-025-00389-z