Heart muscle cell grafts suppress arrhythmias after heart attacks in animal study

August 5, 2012
Heart regenerative medicine researcher Dr. Michael Laflamme of the University of Washington examines beating heart cells under a microscope. Credit: Alice C. Gray

Researchers have made a major advance in efforts to regenerate damaged hearts.

Grafts of human , grown from , coupled electrically and contracted synchronously with host muscle following transplantation in guinea pig hearts.

The grafts also reduced the incidence of arrhythmias () in a guinea pig model of myocardial infarction (commonly known as a attack).

This finding from University of Washington-led research is reported in the Aug. 5 issue of Nature.

The paper's senior author, Dr. Michael Laflamme, said, "These results provide strong evidence that human cardiac muscle cell grafts meet physiological criteria for true heart regeneration. This supports the continued development of human embryonic stem cell-based heart therapies for both mechanical and electrical repair of the heart."

The video will load shortly
Stem-cell derived heart muscle cells were genetically labeled with fluorescent calcium to flash when they contract. By correlating this optical signal from the graft cells with an electrocardiogram -- electrical signals from a recipient's heart -- researchers determined that transplanted human heart cell grafts electrically coupled with the recipient's own heart muscle. Credit: Michael Laflamme and Charles Murry, University of Washington

During a the flow of oxygen-rich blood to the heart muscle is interrupted by formation of a clot, causing death of the down-stream heart muscle and its eventual replacement by . This can cause mechanical problems with filling and emptying the heart, and it can also interfere with the that pace the heartbeat.

In this study, the guinea pigs' hearts had an injury to the left ventricle, the thick walled lower chamber in the heart that pumps oxygenated blood to the body. The injury left a scar and thinned the ventricle, which showed both reduced pump function and greater susceptibility to arrhythmias.

Injured hearts that received the human cardiac muscle cell grafts showed partial re-muscularization of the scarred .

Consistent with previous studies, tests showed that the injured hearts with the human cardiac cell grafts had improved mechanical function.

More surprisingly, these hearts showed fewer arrhythmias than did injured hearts without such grafts.

"We showed a couple years ago that transplanting -derived heart muscle cells improves the pumping activity of injured hearts," said Dr. Michael Laflamme, UW associate professor of pathology and a member of the UW Center for Cardiovascular Biology and the Institute for Stem Cell & Regenerative Medicine.

"In this recent paper," he explained, "we show that the transplantation of these cells also reduces the incidence of arrhythmias [heart rhythm disturbances]."

Frozen specimens are removed from a vat in Dr. Michael Laflamme's lab at the University of Washington, where researchers are working to regenerate damaged hearts with stem cell transplants. Credit: Alice C. Gray

Laflamme and Dr. Charles E. Murry, UW professor of pathology, bioengineering and medicine, Division of Cardiology, were the senior authors of the paper. The lead authors were Drs. Yuji Shiba and Sarah Fernandes in the UW Department of Pathology. Shiba is also from the Department of Cardiovascular Medicine at Shinshu University in Japan.

Because arrhythmias are a major cause of death in patients after a heart attack, Laflamme pointed out, this effect might be clinically useful if proven successful in large animal models as well.

Scientists had been worried that transplanting heart muscle cells derived from embryonic stem cells would promote arrhythmias.

"Instead, they suppress arrhythmias, at least in the guinea pig model," Laflamme and his team were pleased to discover.

While Laflamme and Murry had previously shown that transplanting these types of cell grafts improved pump function in injured hearts, Laflamme noted that it had not been previously determined if the grafts actually coupled and fired synchronously with heart's original muscle.

There was the possibility, he suggested, that they exerted their beneficial effects indirectly, perhaps by releasing signaling molecules, rather than by forming new force-generating units.

"In our study, we discovered that the heart cell grafts do, in fact, couple to the guinea pig hearts," he said.

The research team found the heart cell grafts electrically coupled in all of the normal, uninjured hearts into which they were transplanted, and in the majority of the injured hearts.

The researchers were able to observe this coupling by transplanting human cells that were genetically modified to flash every time they fired. By correlating this optical signal from the graft cells with the electrocardiogram – electrical signals from the recipient heart – the researchers were able to determine whether cell grafts were electrically coupled with the animal's heart.

Explore further: Fruit fly hearts similar to human hearts

Related Stories

Fruit fly hearts similar to human hearts

February 27, 2007

U.S. scientists say Drosophila fruit fly research may lead to new treatments for heart disease, the leading cause of death in industrialized nations.

Heart derived stem cells develop into heart muscle

April 23, 2008

Dutch researchers at University Medical Center Utrecht and the Hubrecht Institute have succeeded in growing large numbers of stem cells from adult human hearts into new heart muscle cells. A breakthrough in stem cell research. ...

Newly discovered heart stem cells make muscle and bone

December 1, 2011

Researchers have identified a new and relatively abundant pool of stem cells in the heart. The findings in the December issue of Cell Stem Cell, a Cell Press publication, show that these heart cells have the capacity for ...

How do you mend a broken heart?

December 22, 2011

Damaged heart tissue is not known for having much inherent capacity for repair. But now, scientists are closing in on signals that may be able to coax the heart into producing replacement cardiac muscle cells. Using a zebrafish ...

Recommended for you

Basic research fuels advanced discovery

August 26, 2016

Clinical trials and translational medicine have certainly given people hope and rapid pathways to cures for some of mankind's most troublesome diseases, but now is not the time to overlook the power of basic research, says ...

New method creates endless supply of kidney precursor cells

August 25, 2016

Salk Institute scientists have discovered the holy grail of endless youthfulness—at least when it comes to one type of human kidney precursor cell. Previous attempts to maintain cultures of the so-called nephron progenitor ...

New avenue for understanding cause of common diseases

August 25, 2016

A ground-breaking Auckland study could lead to discoveries about many common diseases such as diabetes, cancer and dementia. The new finding could also illuminate the broader role of the enigmatic mitochondria in human development.

Strict diet combats rare progeria aging disorders

August 25, 2016

Mice with a severe aging disease live three times longer if they eat thirty percent less. Moreover, they age much healthier than mice that eat as much as they want. These are findings of a joint study being published today ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.