How Does One Mend A Broken Heart?

Current research indicates that it may be possible to “fix a broken heart.” Adult stem cells may be used to help replace damaged heart muscles, heart tissue, valves and establish new blood vessels to supply them.

According to the CDC’s National Center for Health Statistics, heart disease is the number one cause of death of both men and women in the United States.  Because heart muscle cells do not replace themselves naturally, those who have suffered from a heart attack, congenital heart disease, or congestive heart failure have few treatment options.  Adult stem cells, however, offer new hope in the fight against heart disease. Current research indicates that it may be possible to “fix a broken heart.”  Adult stem cells may be used to help replace damaged heart muscles, heart tissue, valves and establish new blood vessels to supply them.  The American Heart Association estimates that 58 million people who currently suffer from cardiovascular disease might one day be cured or treated through stem cell breakthroughs.

Here’s How It Works

Stem cells are the parent cells for all tissues and organs of the body.  Stem cells can be found in a person’s blood, muscles, bone marrow, and organs such as the brain and liver.  Stem cells are also found in umbilical cord and menstrual blood.  The primary role of an adult stem cell is to maintain and repair the tissue in which it is found but stem cells also have the remarkable potential to develop into many different cell types in the body. When a stem cell divides, each new cell has the potential to either remain a stem cell or become another type of cell with a more specialized function, such a heart cell.

One important heart cell is the cardiomyocyte, the heart muscle cell that contracts to eject the blood out of the heart's main pumping chamber (the ventricle). Two other cell types that are important to a properly functioning heart are the vascular endothelial cell, which forms the inner lining of new blood vessels, and the smooth muscle cell, which forms the wall of blood vessels. These two specialized cells are important for developing a new network of arteries to bring nutrients and oxygen to the cardiomyocytes after a heart has been damaged.  Researchers now know that stem cells can be coaxed into developing as new cardiomyocytes and vascular endothelial cells.  Scientists are interested in developing this ability to provide replacement tissue for a damaged heart.

What is the evidence that such an approach to restoring cardiac function might work?

About a decade ago, scientists began testing the effectiveness of stem cells in regenerating heart tissue by simulating heart attacks in mice and rates and then repairing the damage with heart cells grown from stem cells.  In 2001, doctors reported that after they injected adult bone marrow into the damaged wall of the ventricle, these cells led to the formation of new cardiomyocytes, vascular endothelium, and smooth muscle cells, which in turn developed into coronary arteries, arterioles, and capillaries. The newly formed arteries, arterioles and capillaries occupied 68 percent of the damaged portion of the ventricle nine days after the bone marrow cells were transplanted, in effect replacing the dead tissue with living, functioning tissue. The researchers found that mice that received the transplanted cells survived in greater numbers than mice with heart attacks that did not receive the mouse stem cells.

In 2003, sixteen-year-old Dimitri Bonnville became the first human to receive experimental stem cell therapy to revive his damaged heart tissue.  Bonnville had been accidentally shot in the heart with a nail gun while doing home repair, undergone open-heart surgery and suffered a massive heart attack. In lieu of heart transplant surgery, Bonnville’s parents opted for stem cell therapy to repair his damaged heart.  Doctors at the William Beaumont Hospital in Michigan harvested stem cells from Bonnville’s blood. Using a heart catheter, they transplanted the stem cells into the artery that supplies blood to the front of the heart.  Following the procedure, Bonnville experienced significant improvement in heart function.

In 2004, the FDA approved the first clinical trial in the United States to test stem cell therapy for severe heart failure.  Prior to this clinical trial, scientists in Brazil had already tested the treatment on fourteen patients in Brazil. That study, published in Circulation Research, showed that the procedure is safe and significantly improves heart function.  “We saw significant improvements in exercise capacity,” said Emerson Perin at the Texas Heart Institute in Houston, Texas. “This is measured in terms of peak oxygen capacity, which went from 17 percent to 24 percent in treated patients.”

On February 11, 2009, officials with the University of Louisville and Jewish Hospital & St. Mary’s Healthcare Inc. announced that they will be the first to host to an FDA-approved clinical trial that targets heart disease with the use of cardiac stem cells.  A group of twenty patients with advanced heart disease who are already undergoing bypass surgery will be recruited for the study.  During surgery, physicians will remove a small piece of heart tissue and send it to Harvard University, where the cardiac stem cells will be extracted. After a three- to four-month recovery period, the stem cells will be injected into scar tissue on the hearts of the patients.  Physicians will follow the patients’ progress for at least a year, measuring heart function and blood flow. The dimensions of the heart, which becomes enlarged after heart failure, also will be measured, along with the size of scar tissue, said study leader Roberto Bolli, distinguished chair in cardiology at the Jewish Hospital Heart and Lung Institute.

A stem cell company in Columbia, Md., on February 12, 2009, reported the final two-year results for its Phase I clinical trial evaluating the safety of a stem cell treatment for acute myocardial infarction (heart attack). The treatment, called Prochymal, is a proprietary formulation of adult stem cells designed to provide therapeutic benefit by controlling inflammation, promoting tissue regeneration, and preventing scar formation.  The double-blind, placebo-controlled study, which evaluated safety and preliminary efficacy in 53 patients, found heart attack patients receiving the intravenous therapy had lower rates of adverse events and significantly improved heart function.  Although stem cell therapy to repair damaged hearts is still being tested, most studies that have been conducted to date show that stem cell therapy reduced the impact of a heart attack and improved the heart's ability to pump.  A 2007 article in the International Journal of Cardiology, for example, reported on a study that divided 70 cardiac patients into two equal groups: One group received injected stem cells and the other group received a placebo.  Six months later, the patients treated with stem cells had a significant improvement in left ventricular pumping, and in the control group, there was no improvement. Twenty-five patients experienced complications, but none died.

With these advances in the use of stem cell therapy to repair damaged heart tissue, another recent welcome finding is the discovery that a popular statin drug may help stem cells perform this job even more effectively.  In a paper published in the January 2009 issue of Circulation Research, scientists at the University of Buffalo’s Center for Research in Cardiovascular Medicine reported that Pravastatin, a statin drug used to treat cholesterol, may have an added benefit of preventing the development of heart disease by regenerating diseased heart tissue.  The drug appears to mobilize bone marrow progenitor cells – blood stem cells that are able to transform into many different types of cells -- which infiltrate the heart and develop into cardiac muscle cells, thus improving cardiac function.  “The finding that a drug with an excellent safety profile used widely to lower blood cholesterol is effective in improving cardiac function in hibernating myocardium is a welcome finding,” said Gen Suzuki, M.D., Ph.D., UB research assistant professor of medicine and first author on the study.

In addition to being able to repair heart damage through the transplantation of stem cells into the affected area, doctors have been able to grow heart parts in the lab to eventually be placed in a damaged heart. In 2007, Sir Magdi Yacoub, a world famous heart surgeon based at Imperial College London and  a team of physicists, pharmacologists, cellular and clinical scientists, developed heart valve cells by taking adult stem cells from bone marrow. They used collagen to hold the valve tissue in shape as it grew into one-inch disc-shaped valves.  Although plastic heart valves do exist, stem cell-grown valves offer a distinct advantage: "[B]ecause the patient's own stem cells are used it eliminates the problem with rejection that happens when a heart has been donated by another person."
Presenting at the American Heart Association's (AHA) annual scientific sessions in New Orleans in November 2008, cardiac surgeon Dr. Ralf Sodian reported that his team had also used stem cells to create tissue-engineered heart valves.  His team stored stem cells derived from umbilical cord blood for twelve weeks and then seeded them onto eight heart valve scaffolds which then grew tissue that nearly mirrored human heart valve tissue.  Adult stem cells collected at birth from the umbilical cord may help doctors fashion new heart valves for children born with heart valve defects. The tissue-engineered valves would have the advantage of growing with the child, said researchers at the University Hospital of Munich. "If we replace a valve in a child, they will need surgery several times in their lifetime, because they will grow out of the devices, so the ultimate goal is to have a construct which is able to grow with the child and only have to do the surgery once," said Dr. Sodian.  In addition, stem cell-based valves offer the advantage of not experiencing the wear and tear issues related to metal and plastic valves.

In addition to the creation of heart valves, scientists have also discovered a way to generate functioning, beating heart cells from stem cells.  In February 2009, researchers at the University of Wisconsin-Madison announced that they had taken skin cells and grown them into pulsing heart cells.  In Circulation Research, Timothy Kamp, co-director of UW’s Stem Cell & Regenerative Medicine Center, reported that the reprogrammed heart cells made in the laboratory performed some key functions of the heart cells inside our bodies. They generated electrical pulses, and in response to these pulses, they contracted.  It is the collective contraction of all these cells that enables the heart to beat. "It's an encouraging result because it shows that those cells will be useful for research and may someday be useful in therapy,'' said Kamp.  "If you have a heart failure patient who is in dire straits — and there are never enough donor hearts for transplantation — we may be able to make heart cells from the patient's skin cells, and use them to repair heart muscle. That's pretty exciting."