A microscope being used in research
Stem cells promise to mend broken hearts, young and old

A broken heart can’t fix itself—at least not yet.

Consider what happens after a heart attack, when the cardiac muscle gets damaged. The heart does such a poor job at regenerating new muscle that scar tissue quickly develops in its place. The problem: that scar tissue doesn’t contract like normal tissue does, and the heart’s capacity to pump blood dramatically weakens. The result often is heart failure.

At that point, the only real option is a whole organ transplantation. But waiting lists are long, supplies are short, and patients lucky enough to receive a new heart need close follow up and lifelong immunosuppression treatment so their bodies do not reject the new organ.

Stem cell therapy could change all that by aiding heart regeneration and removing the need for a transplant in the first place. 

“Hope is on the horizon for heart failure, a major cause of death in this country” said NIH Director Francis Collins, M.D., Ph.D.. “Early experiments suggest that a patient’s heart could even be re-built using his or her own induced pluripotent stem cells. This personalized re-built heart would make transplant waiting lists and anti-rejection drugs obsolete.”

Induced pluripotent stem cells (iPSCs) are generated from adult cells, usually from the skin or blood, and reprogramed to an embryonic-like state.

study  in the journal Nature, offered the first glimpse into how this might work. Researchers showed that injecting the hearts of monkeys with cardiac muscle cells (called cardiomyocytes) derived from iPS cells revitalized the hearts of the animals and helped them recover from a heart attack.

The study’s main author, Yuji Shiba, M.D., Ph.D., head of the Department of Biotechnology and Biomedical Engineering, Shinshu University in Japan, will discuss the progress of this research at the upcoming Cardiovascular Regenerative Medicine Symposium on September 27-28, at the NIH.

Most studies using cardiomyocytes derived from human iPS cells have been done across species, what are known as xenogeneic transplantation models. But in Shiba’s study, the researchers induced heart attacks in five macaques and then “transplanted primate iPSCs-derived cardiomyocytes into the infarcted heart of the same species,” the author explained.

After 12 weeks, the monkeys’ immune systems tolerated the new cells, which replaced around 16 percent of the damaged tissue and helped the heart contract better and pump blood more efficiently, said Shiba.

For Michael A. Laflamme, M.D., Ph.D., at University Health Network in Toronto, the study “provides exciting proof of concept for the use of iPSC-derived cardiomyocytes (iPSC-CMs) in treating post-myocardial heart failure,” although he said it also highlights some significant hurdles, such as an increased incidence of irregular heartbeats, or arrhythmias.

The iPSCs were grown from the skin of a single monkey, which was a close genetic match to the other five. The stem cells partially built muscle in the infarct scar and improved its ability to contract.

These studies add to the growing body of research in cardiovascular repair and regeneration, an important part of the National, Heart, Lung, and Blood Institute (NHLBI) research priorities.

Laflamme’s lab is testing the injection of cardiomyocytes in pigs, and the results, which he will present at the NIH symposium, so far track with those of Shiba. 

“We’re also seeing arrhythmias in the pig model, and I’d say that they’re qualitatively worse in the pig than what we and others have previously reported in non-human primates,” said Laflamme. “We think that it is because the pig’s heart rate is much closer to that of humans.”

The pig model, Laflamme and his colleagues say, might be better suited to address some remaining challenges, such as overcoming arrhythmias and finding the best way to deliver the cardiomyocytes to the heart.

The wide interest in these studies speaks to the high expectations the public has for the use of stem cells in regenerative medicine and in the promise it all holds for age-related conditions like heart failure.

The same excitement is brewing for the use of stem cells in treating very young patients with heart disease.

In the United States, nearly 1,000 babies are born each year with hypoplastic left heart syndrome (HLHS), the most complex of cardiac birth defects. HLHS limits the heart’s ability to pump blood to the body, and until a few decades ago, was always fatal.

Now, it can be treated with several open-heart surgeries before age three, but still too many children die or require a transplant. A first-in-children randomized clinical study aims to improve these odds by injecting adult stem cells derived from bone marrow into the babies' hearts during open-heart operations.

Last December, Sunjay Kaushal, M.D., Ph.D., lead researcher for the study, and chief of pediatric cardiac surgery at the University of Maryland Medical Center, administered the experimental injections to a four-month-old who was missing nearly half his heart.

“The premise of this clinical trial is to boost or regenerate the right ventricle, the only ventricle in these babies, to make it pump as strongly as a normal left ventricle,” Kaushal said. “With the stem cell injections, the right ventricle is rejuvenated.” That’s because the cells are much like biological factories, he explained, that are able to secrete “good factors” [for instance, proteins that aid regeneration] to the right ventricle.

This type of stem cell-based therapy will not cure the underlying cause of HLHS, Kaushal said, but it may realign the myocardium to make it more durable so it can continuously pump blood.

The trial has enrolled three patients, including the four-month-old baby, who are doing well and have had no safety issues after their surgery, according to Kaushal. Phase I of the study will be completed in early 2018.

“Once we have determined safety, feasibility, and efficacy, we hope to use this therapy for other complex congenital heart disease conditions in order to avoid unnecessary operations, including heart transplantation,” said Kaushal. From children, the hope is that the research could move to adults. “This therapy will be used in adults with congenital heart disease and we feel it will be a game-changer for these patients.”

Learn more

Cardiac repair with pluripotent stem cell-derived cardiomyocytes: Proof of concept but new challenges

Cardiomyocyte Regeneration. A Consensus Statement

First U.S. babies treated in unique study of adult stem cell therapy for congenital heart disease

Cardiac Progenitor Cells Enhance Neonatal Right Ventricular Function After Pulmonary Artery Banding