For the first time, researchers have used stem cells from a patient’s own heart to repair the damage to the muscle that occurs during heart attack.
Dr. Eduardo Marban, director of the Cedars Sinai Heart Institute, and his team report in the journal Lancet that 17 patients who received an injection of their own heart cells grown from their stem cells saw the scarring on their hearts shrivel by 50% over a year. Eight patients who received usual care had no change.
During a heart attack, some of the heart’s muscle is cut off from its oxygen supply, so within seconds these cells start to die. The body’s immune system treats the change like a trauma and begins to wall off the dying tissue, creating an ever-thickening layer of scarring; eventually, the scar tissue hampers the heart’s ability to pump blood efficiently throughout the body. Keeping this scarring to a minimum, or even reversing it is the Holy Grail of heart attack research: maintaining as much healthy and active heart muscle as possible increases patients’ chances of recovering quickly and completely.
“Heart disease is still the number one killer of men and women, so there is a dire need for new therapies to be tested,” says Dr. Deepak Srivastava, director of the Gladstone Institute Cardiovascular Disease, who is a leader in heart stem-cell research and was not involved in the current study. “I applaud them carrying through with a clinical trial, which is great.”
The heart has a natural ability to fix minor defects by regenerating new muscle cells to replace dying ones. About 1% to 2% of heart cells die each year, and are replaced this way. This process can’t come close to regenerating the one-third of heart muscle that is typically affected by a heart attack, however, so Marban and his team decided to give the process a boost. The researchers extracted some of the naturally healing stem cells from the heart and nurtured them in a lab dish. The hope was to inject a large enough population of the cells back into the heart to trigger a broad-scale repair of the muscle after heart attack.
“We were gratified to see that the scars shrank in patients who had gotten the cells,” Marban says. “Not only that, but these patients also had a big increase in living heart muscle. The regeneration of living tissue, or regrowth of lost tissue, which is what we were able to achieve, is encouraging.”
All of the patients were enrolled in the trial within 1.5 months of having a heart attack, and had their hearts scanned with an MRI. Seventeen of the patients had a biopsy of their heart tissue so the researchers could extract the heart’s stem cells and expand them in the lab; the researchers then re-infusing 12 million to 25 million new heart cells into each patient’s heart artery 1.5 months to 3 months later. The control patients received standard care of medications and monitoring to recover from their heart attack.
At six months and again at one year into the study, Marban and his colleagues took additional MRIs of the patients’ hearts, to measure any changes in the size of their scar tissue. The patients who had received the heart cells showed markedly smaller scars and more living tissue over time, compared with those who received standard therapy. In fact, new tissue formation increased by 60% on average, compared with scar shrinkage.
Unfortunately, however, the patients did not show any change in heart function, as measured by the ejection fraction, or the ability of the heart to pump blood. In patients who got the stem cells, their ejection fraction went from 39% at the start of the study to 41% a year later; healthy hearts pump at about 50% or greater efficiency.
But Marban isn’t discouraged by that, noting that although he wasn’t able to show that the heart functioned better overall in the stem-cell patients, he did find that in the areas where the scars had shrunk, the muscle appeared to be working more efficiently. “When you zoom in and look at regional function, there was big improvement,” he says. “We believe that the changes we see in the amount of scar tissue, even though it’s dramatic and unmistakable and significant, still aren’t enough to tilt the balance toward complete repair of the heart.”
Will it take more cells, or more time, or different types of cells to generate that type of complete repair? That’s impossible to tell from this study, but the results are encouraging enough to trigger more work into such cell-based treatments. “This is part of a series of important steps toward ultimately moving to cell-based therapy that will someday create new muscle in the heart,” says Srivastava.
Future studies could answer some critical questions about exactly how the infused cells are helping to shrink scars and prompt the growth of new heart muscle. Srivastava notes that it’s unlikely that the new cells are turning into heart muscle themselves, but are more likely helping existing heart muscle generate new tissue. If that’s the case, then researchers can refine the technique to help heart attack patients months or even years after their event to repair their scarred hearts. “The real objective is to offer treatment for people who have a long-standing injury to the heart, and more severe heart disease,” says Marban.