Scientists Uncover the Heart Cells’ ‘Protective Code’ That Prevents Cardiac Regeneration

Scientists have identified a way to "awaken" the heart's ability to repair itself after a heart attack. A new study has revealed that heart muscle cells rely on a specialized protective mechanism that prevents them from changing their identity, but blocking this mechanism could help trigger cardiac regeneration.

Unlike the skin and certain other tissues, the adult human heart has very little capacity to regenerate damaged cells on its own. For years, researchers have been working to reprogram heart muscle cells so they can produce new, healthy tissue following a heart attack.

However, cardiomyocytes—the cells responsible for the heart's contractions—are highly stable. They have evolved to perform their function efficiently and strongly resist attempts to alter their identity.

Researchers from the Sanford Burnham Prebys Medical Discovery Institute and the Johns Hopkins University School of Medicine have now identified one of the key mechanisms behind this resistance. Their study, published in Nature Communications, found that a protein called CHST7 acts as a molecular "guardian" of cellular identity.

CHST7 belongs to a family of proteins involved in glycosylation—the process of modifying other molecules by attaching sugar groups. The researchers found that CHST7 is one of the strongest barriers to cellular reprogramming in both mouse and human heart cells.

The study showed that CHST7 exerts its effects through the cell-surface receptor CD44, enhancing its signaling activity. This, in turn, alters the activity of the protein JUNB, which regulates gene expression.

Together, CHST7, CD44, and JUNB form a regulatory system that helps cells maintain their original identity. They control access to DNA regions that regulate gene activity by keeping genes responsible for cellular stability active while blocking those required for reprogramming.

"By understanding how heart cells protect their identity, we can identify ways to overcome these barriers and enhance recovery after injury," the researchers said.

Further experiments identified another important molecule—an enzyme called PIP4K2C, which also helps maintain cellular stability. When the researchers simultaneously blocked PIP4K2C and induced reprogramming in the hearts of mice, the regenerative response improved significantly.

One month after a heart attack, mice receiving the combined treatment recovered heart function to about 58.6% of normal pumping capacity, compared with 24.9% in animals treated with cellular reprogramming alone.

The researchers believe the findings could pave the way for new therapies to repair heart damage. Understanding why heart cells resist changing their identity may ultimately help scientists develop treatments that enable the heart to regenerate more effectively after a heart attack.

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