Cell paper outlines heart’s regenerative capacity, holds promise for new therapies

GRAND RAPIDS, Mich. (June 12, 2015)—For the first time, scientists have shown that the adult human heart generates new muscle cells in multiple sites throughout the organ and experiences cellular turnover several times throughout an average lifespan.

The paper, Dynamics of cell generation and turnover in the human heart, was published June 11 online in Cell and demonstrates that new cardiomyocytes, or heart muscle cells, are continuously generated throughout the heart but hit a threshold of 3.2 billion cells at one month of age. This fixed number indicates that new cells only replace those that die off and that growth of the heart is due to enlargement of individual heart cells, rather than an increasing number of cells. The team also showed other cells that line the heart’s vessels only completely replenish eight times throughout an average human lifespan.

Unlike many cells in other areas of the body, cardiomyocytes do not have a high turnover rate, making it difficult to heal when the heart sustains damage. Uncovering the mechanisms behind cardiomyocyte regeneration could lay the foundation for the development of new therapies that harness the heart’s regenerative capabilities to heal itself.

The work is a result of collaboration between Stefan Jovinge, M.D., Ph.D., director of the DeVos Cardiovascular Research Program (a joint effort between Van Andel Research Institute and Spectrum Health) and a professor at Sweden’s Lund University, and Karolinska Institute’s Jonas Frisén, M.D., Ph.D., Olaf Bergmann, M.D., Ph.D., and Henrik Druid, M.D.

The new study builds on the group’s 2009 Science paper, which demonstrated that the adult heart is indeed capable of generating new muscle cells, albeit slowly at about 1 percent annually at age 25. This turnover rate decreases as a person ages, dropping to about 0.45 percent by age 75. The new paper expands on the 2009 findings by further defining where this regeneration occurs and how often.

“In our previous paper, we showed an unequivocal generation of heart muscle cells in the adult human heart. This led to a lot of questions about the nature of the adult generation of cardiomyocytes,” Jovinge said. “Is the generation of cardiomyocytes restricted and generated from certain locations in the heart? Is the heart increasing in size mainly by adding more cells? And how does the growth and expansion of the other cells in the heart occur? The prospect of using the inherent capacity to generate heart muscle cells in adults to make the heart repair itself requires answers to these questions. This paper does that.”

Heart failure is a chronic condition marked by a reduction in the heart’s ability to pump a sufficient amount of blood throughout the body. More than five million people in the U.S. have heart failure and about half of those who develop the condition will die within five years of diagnosis, according to the U.S. Centers for Disease Control and Prevention. Once diagnosed, treating heart failure is a lifelong process and involves drug therapies or invasive surgery such as a heart transplant, neither of which actually repair damage to the heart.

“Our findings open avenues for more research on individual heart muscle cells to find the source for this regeneration,” Jovinge said. “It brings us one step closer to developing regenerative therapies for heart diseases.”

Current work in Jovinge’s laboratory at Van Andel Research Institute focuses on finding the individual cell types responsible for the generation of new heart muscle cells and understanding how this process is regulated, which holds promise for devising ways to stimulate the heart to generate new muscle cells. Once this process is established, Jovinge’s team plans to develop a treatment to help the heart mend itself. In addition to leading Van Andel Research Institute’s Laboratory of Cardiovascular Research, Jovinge also is medical director of research at Spectrum Health Frederik Meijer Heart & Vascular Institute, where he directs a clinical program aimed translating his laboratory findings into new therapies for patients with heart failure and other cardiovascular diseases.

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