When you cut yourself, your skin heals. When you break a bone, the bone heals. When you have a heart attack, the heart muscle does not heal. But it has been known for a while that a small amount of heart muscle cell proliferation can occur.

This heart muscle cell replication replenishes the heart muscle that is lost to normal wear and tear over the years.

Dr. Hesham Sadek and colleagues at UT Southwestern Medical Center have identified the cells that replicate to replenish heart muscle. This discovery is a big step toward the ultimate goal of getting heart muscle to repair itself following a heart attack.

“We identified a cell that generates new heart muscle cells. This cell does not appear to be a stem cell, but rather a specialized cardiomyocyte, or heart muscle cell, that can divide, which the majority of cardiomyocytes cannot do,” said Sadek, assistant professor of Internal Medicine and with the Hamon Center for Regenerative Science and Medicine.

Previous research by UT Southwestern scientists revealed that it is the highly oxygenated environment of the heart that prevents most heart muscle cells from dividing. The researchers reasoned that the cells that do divide must exist in a lower oxygen environment, which is a condition called hypoxia. They then devised a technique to identify and trace the lineage of hypoxic cells. That technique led them to the identification of the proliferating cells within heart muscle.

“For decades, researchers have been trying to find the specialized cells that make new muscle cells in the adult heart, and we think that we have found that cell,” said Sadek, senior author of the study, which appears online in Nature.

“Now we have a target to study. If we can expand this cell population, or make it divide more, then we can make new muscle cells. This is what this cell does naturally, and we can now work toward harnessing this ability to make new heart muscle when the heart has been damaged.”

The researchers found hypoxic microenvironments with proliferating cells scattered throughout the heart muscle. They found the rate of formation of new cells to be between 0.3 percent and 1 percent annually.

“This is exciting work from both scientific and methodological standpoints,” said Joseph Hill, chief of the Division of Cardiology and professor of Internal Medicine at UT Southwestern, who holds the James T. Willerson, M.D. distinguished chair in Cardiovascular Diseases and the Frank M. Ryburn, Jr. Chair in Heart Research. “Dr. Sadek’s discovery points to a novel mechanism of cell-cycle control in cardiac myocytes and lends credence to the potential for regenerating – rebuilding – the diseased heart.”

The new technique used to find the regenerative cells, a process called fate mapping, is an equally important development that may prove useful for distinguishing similar regenerating cells in other organs, as well as in cancers, the researchers said.

Traditional fate mapping, which is somewhat like developing a family tree for cells, labels cells based on the expression of a certain gene. That didn’t work for the hypoxic cells, which are mainly regulated at the protein level rather than the gene-expression level. Instead, the researchers developed a sophisticated protein-tracking technique.

“This fate-mapping approach, based on protein stabilization rather than gene expression, is an important tool for studying hypoxia in the whole organism. It can identify any hypoxic cell, not just cardiomyocytes, so this has broad implications for cellular turnover in any organ, and even in cancer,” said Sadek, whose lab focuses on cardiac regeneration and stem cell metabolism.