A new study, published this week in points the way to a treatment that may one day make heart transplants obsolete. A team of researchers, led by pathologist Charles Murry of the University of Washington, injected human embryonic stem cells into the hearts of five , a kind of monkey, and saw their hearts regrow lost muscle.
"At First We Couldn't Believe It"
Scientists knew stem cells could regenerate heart tissue in rodents, but macaques (which are a type of monkey) are closer to humans in their size, physiology, and heart rate. Whereas a rat's heart beats 400 times per minute, a macaque's beats 115 times per minute, much closer to a human's 70 beats per minute. Carrying out the experiments on primates "is truly a major achievement," says Richard Lee, who studies cardiac regeneration at the Harvard Stem Cell Institute (he wasn't involved in the current study).
The scientists injected about a billion stem cells into each monkey's heart. Growing so many cells required a lot of petri dishes, with a total surface area equivalent to 30 medium-size Domino's pizzas for every monkey, Murry says. "We had incubators stacked floor to ceiling with cell cultures. The actual volume of the cells is about a milliliter and a half, but they need more room when they're growing."
Monkeys and other wild animals almost never develop heart failure naturally, so to do the experiment, Murry's team had to induce heart failure. Basically, they stuck a catheter into each monkey's coronary artery, and inflated a small balloon to stop blood flow to the heart for 90 minutes, similar to the way a blood clot would prevent blood flow to a human heart. The heart cells downstream from the blockage died, and the scientists injected stem cells there. After several weeks, the monkeys were euthanized and autopsied.
Human cardiac muscle graft (green fluorescent protein immunostain) in macaque heart contains myofibril bundles with well formed sarcomeres (alpha-actinin, red). The host heart muscle around the graft stains red. Credit: Veronica Muskheli.
In two control monkeys, who weren't injected with stem cells, the bottom tip of the heart had a zone of white discoloration where scar tissue had formed—the heart hadn't healed. But in the monkeys that received the stem cell treatment, new muscle grew up to 0.6 inches wide and was visible to the naked eye. "At first we couldn't believe it," Murry says. "These grafts were 10 times bigger than anybody in the world has done before."
The grafts were also intersected by new blood vessels that had sprung up to deliver oxygen and energy to the new muscle tissue, implying that the grafts could continue to grow and thrive.
The Big Step
That's promising news, but the treatment is not ready to be tested in humans yet. "There are still big challenges in the laboratory, and whether they will break through with clinical success in the next decade is still an open question," Lee says.
ECGs of the monkeys' hearts revealed that the graft cells weren't beating in perfect time with the monkeys' natural cells. "We never saw this in the small animals, I think because their heart rates are too fast," Murry says. "At first we were depressed. Then we took a step back and thought: Well, that's why we did the study."
Murry thinks that the young muscle cells are too immature to electrically sync with the older heart cells. The problem may be avoided by injecting slightly more mature cells next time. It's also possible that an implanted pacemaker or defibrillator could keep the cells beating together, says Linda Van Laake, a cardiologist at the University Medical Center in Utrecht, Netherlands.
Another handicap is that the team used human embryonic stem cells that don't match the patient's DNA. That means patients who use this treatment would need to take immunosuppressants for the rest of their lives, to prevent the body from attacking the graft as a foreign substance. "Immunosuppression is still better than having heart failure," Murry says. And it's still better than dying on a waiting list for a heart transplant.
In the future, it may be possible to take snippets of a patient's skin or blood and turn those cells into "induced pluripotent stem cells". Those stem cells could presumably regenerate heart muscle without the risk of being rejected by the body. The challenge there will be to speed up the culturing process; it takes weeks or months to generate enough cells for the injections.
Murry is hopeful that if those hurdles can be overcome, stem cells could become a viable treatment for heart failure within 10 years. "The bottom line is, it looks like this works pretty well in a monkey. And I think if we can do this in a monkey, we can do it in a human."