The smallest elements of our bodies may be a secret cure
for heart disease
“THEY THOUGHT THEY WERE JUST like everyone else. Until they woke with incredible abilities.”
That’s how NBC promoted its new drama series Heroes, about a group of ordinary people who discover skills not usually found in the mortal repertoire: one can see the future, another can fly, and one character, a perky blonde cheerleader, learns that she is “unbreakable.” In the drama’s trailer, she rushes into a burning building to save a life, and when a firefighter rips away her scorched uniform, he finds no damage to her shapely arm. Instant tissue regeneration is her particular gift.
In science fiction, self-repairing bodies are a stock device, as common as, well, perky blondes. But in the world of science fact, tissue regeneration is more than just a paranormal plot device. Today, doctors are hopeful that therapies that encourage tissues to repair themselves will become a key treatment in the fight against heart disease.
At the center of these hopes are stem cells. At first description, stem cells do sound like the stuff of science fiction. They are “undifferentiated” cells — blank slates that have the ability to become other types of function-specific cells — blood cells, liver cells, brain cells, and so on. It sounds fantastic, but it makes sense when you consider the basic biology.
“You and I are the product of two cells, our father’s sperm and our mother’s egg,” says Dr. James T. Willerson, medical director and president elect of the Texas Heart Institute in Houston. “Those two cells became everything that we are, and aren’t — the way we look, our height, our intellect, our brain. We’re all stem cell products.”
Stem cells aren’t active only when the human body is forming inside the womb, though. They exist throughout the body, in bone marrow, blood, and fat, and are called into action whenever there’s a need for repair. So while research into the use of embryonic stem cells has been highly controversial, the therapeutic use of “adult stem cells” — stem cells that are extracted from an adult’s body, for the patient’s own use — poses less of an ethical dilemma.
The area of heart disease is where stem cell research has progressed the furthest, says Dr. Amit Patel, director of cardiac stem cell therapies at the McGowan Institute for Regenerative Medicine at the University of Pittsburgh Medical Center. Part of the reason for that, according to Patel, is the great need for therapies to treat heart disease, the top cause of death for both men and women in the United States. Another is that the task stem cells are required to perform in cardiac treatment is less complicated than with other diseases. “In diabetes, for example, you’re trying to make an insulin-producing cell and regulate metabolism,” he says. “The level of complexity of what we’re doing in the heart is a level simpler. We’re just trying to make a pump stronger and work better.”
Ironically, thanks to advancing medical science, there are a lot of pumps — or hearts — in need of shoring up. Heart attacks are less fatal now than they used to be, says Dr. Janet Wright, a cardiologist in Chico, Calif., who sits on the board of trustees of the American College of Cardiology. The most common heart attacks are those caused when cholesterol plaques rupture and lead to the clotting of an artery. Starved of the oxygen that blood delivers, the heart muscle starts to die. For patients who receive care in time, doctors can now do a great deal to limit the damage to the heart and get the blood flowing again, with treatments ranging from pharmaceuticals to surgery. “That’s a very satisfying part of one’s career,” Wright says, “to charge in, in the midst of a heart attack, open up an artery, and make the pain go away.”
But one aftereffect for heart attack survivors is a weakened heart. The heart muscle sustains damage while it is oxygen deprived, and if it becomes weak enough, this can lead to heart failure. (Though heart failure sounds like game-over, it’s actually the term that’s used for a heart that’s failing, rather than one that’s failed.)
In 2000, Willerson and his research partner, Dr. Emerson Perin, traveled to the Pro-Cardiaco Hospital, in Rio de Janeiro, Brazil, where many patients who had sustained heart attacks were living with heart failure. “The normal-shaped heart is fist sized,” says Willerson. “Their hearts were basketball sized.”
Patients with heart failure have an enlarged heart with reduced force of contraction. And indeed, Willerson says, “their hearts were contracting very weakly, and causing them to be very short of breath with little effort. They had no energy, they were unable to work, and they were likely to die rather rapidly.” These patients were unlikely to receive transplants, so they were desperate. Willerson believed that an injection of stem cells from each patient’s bone marrow would help the heart grow stronger. The Perin-Willerson team spent nine months convincing the authorities in Brazil to give the novel therapy a chance.
After the procedure was approved, the Perin-Willerson team harvested 30 million stem cells from each patient’s bone marrow and injected the cells directly into 15 sites in the heart. The results were promising: after two months, their hearts were stronger, as measured by the amount of blood pushed through the heart, and the patients reported more energy and less shortness of breath — not enough to go out and run a marathon, but enough to be better able to carry on the daily activities of life. Willerson and Perin then moved on to a larger group of patients in Brazil and are now trying the same treatment with 30 patients in Houston.
This was the first trial in the world in which patients with prior heart attacks and severe heart failure were treated with their own bone marrow–derived stem cells. Other trials have shown similar benefits from bone marrow–derived stem cells given to patients with their first heart attack. The big question is, what exactly do the stem cells do to strengthen the heart muscle?
The University of Pittsburgh’s Patel, who has also conducted trials that involve injecting stem cells into weakened hearts, offers several possible explanations: The stem cells could be transforming themselves into new blood vessels or new heart muscle, or they could be latching on to weakened muscle to strengthen it. Or they could act like a “homing beacon” for the body’s own natural self-repair mechanisms.
“After a heart attack, the heart sends out an SOS message that it’s been damaged and tries to recruit stem cells to it,” explains Dr. Marc Penn, director of the Bakken Heart-Brain Institute at the Cleveland Clinic, which is studying this particular process. In response to this signal, the bone marrow releases stem cells that go to the heart and attempt to repair the damage. But the heart issues this SOS for only a short time — not long enough to get enough stem cells on the scene to repair the damage. The addition of millions of stem cells into the area via injection could allow the self-repair process to continue for a longer time.
Patel, among others, believes that all three factors play a role in the success of stem cell therapies, but more research is needed to know for sure. The task for doctors now is not only to understand exactly how stem cells do the things they do, but also to learn which types of stem cells are best and what is the best way — and the best time — to deliver them to the heart. Must they be injected directly into the heart, or do stem cells delivered via an injection anywhere in the body work just as well? Is it best to inject stem cells during a heart attack, or afterward?
All these questions and more are being studied in laboratory animals and small groups of human volunteers. Eventually, treatments will be tested in larger groups of human patients (there have already been randomized trials of 200 European patients), and if stem cell–based therapies continue to show their early promise, they could become a common cardiac treatment.
“Got those cells for me yet?” It’s a question Wright hears all the time from one particular patient who suffers from heart failure and who also sits on the independent citizens oversight committee of the California Institute of Regenerative Medicine, which helps distribute money for stem cell research. “It’s heartbreaking,” she says. “I tell him, I’m paying attention to the research, and as soon as there’s a clinical trial that he might participate in, I’ll phone him myself.” She won’t guess how long it might take for stem cell treatments to become widely available.
Others are more willing to talk time. “We’re just at the beginning of a 20-year journey,” says Dr. Stanton Gerson, director of the National Center for Regenerative Medicine, a partnership of Case Western Reserve University, the Cleveland Clinic Foundation, and University Hospitals of Cleveland that is studying non-embryonic stem cells to treat heart disease and other illnesses. Patel believes that fully approved treatments are five to seven years away. Penn says seven to 10 years.
However long the time frame looks, there’s consensus on one thing: these treatments will not be widely available tomorrow. But the good news, says Wright, is “there’s hope, for people who are suffering now, for our children, and definitely for our grandchildren.”
And so for the rest of us, for the time being, self-repairing hearts and self-repairing tissue will remain a plot device in science fiction, the province of unbreakable cheerleaders on a television drama. But eventually we may wake up to find that science has made that incredible breakthrough of self-repairing tissue — and a self-repairing heart — available to us all.
— Alison Stein Wellner
Preventive Medicine
The promise of stem cell research offers hope to heart attack patients in the future, but what does that mean for all of us today? We should work as hard as we can to avoid heart trouble in the first place. “We shouldn’t be eating our cheeseburgers as much as we do,” says Dr. Marc Penn, of the Bakken Heart-Brain Institute at the Cleveland Clinic. In fact, that will be true even when stem cell therapies are available, because about half of all people who suffer their first heart attack will not make it to the hospital to receive stem cell therapy.
Reduce your chances of developing heart disease by quitting smoking, getting more exercise, eating better, watching your weight, and keeping tabs on your blood pressure, cholesterol, and blood sugar. You can learn more about heart health by visiting the American Heart Association at americanheart.org.
— A.S.W.
