The heart is a vital organ—only one to a customer. Limited repair techniques are available to repair damaged ones; however, a new UCLA study has found that the heart has a limited capacity to generate new muscle. The findings could lead to new research regarding the regeneration of heart muscle to repair damage caused by disease or heart attack. The study was published online on May 29 in the Proceedings of the National Academy of Sciences.
Researchers from UCLA's Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research report that their study is the first to directly measure limited division in the cells that comprise heart muscle (cardiomyocytes). They proved that these cells do divide; however, such cell division is rare. They note that the discovery resolves an important recent controversy regarding whether the heart muscle has the power to regenerate.
It was initially believed that cardiomyocytes were unable to reproduce themselves and that their total number was determined at birth. However, research over the past two decades has shown that there is a limited proliferative (replication) activity of these cardiac cells; however, at present there is no clear agreement within the scientific community as to how and why. Some researchers have used carbon dating to detect the age of cardiomyocytes in humans to determine whether they divided after initial fetal development; however, the accuracy of this technique is a topic of debate. Other investigators have published theories that the heart had a very high proliferative ability, but recently many of those studies have been questioned because other researchers were unable to reproduce the data. Indirect methods of measurement, which are complex and inaccurate, have further confounded a consensus.
Study leader Reza Ardehali, assistant professor of cardiology, and his colleagues developed an innovative genetic approach called the mosaic analysis with double markers (MADAM) mouse model. With this rodent model, they found limited, life-long, symmetric division of cardiomyocytes as a rare event. It occurs in fetal mice; however, decreases significantly after the first month of life. Daughter cardiomyocytes, which are the products of this rare cell division, also divide on rare occasions; this process has not been previously shown before. In addition, inducing a myocardial infarction (heart attack) in the mice did not increase the rate of cell division as a response to repair the muscle damaged by the heart attack.
The investigators note that their study is the first to directly show that cardiac cells divide. They also note that no stem cells involved in this process, and that the myocytes are able to divide symmetrically; division of cardiomyocytes is limited to less than 1% per year. “This is one of the most convincing and direct ways of showing that the heart has a very limited regenerative power,” explained Dr. Ardehali. He added, “This is a very exciting discovery because we hope to use this knowledge to eventually be able to regenerate heart tissue. The goal is to identify the molecular pathways involved in symmetric division of cardiomyocytes and use them to induce regeneration to replenish heart muscle tissue after disease or injury.”