Heart-muscle patches made with human cells improve heart attack recovery

January 10, 2018, University of Alabama at Birmingham
Credit: CC0 Public Domain

Large, human cardiac-muscle patches created in the lab have been tested, for the first time, on large animals in a heart attack model. This clinically relevant approach showed that the patches significantly improved recovery from heart attack injury.

The results are a step closer to the goal of treating human attacks by suturing cardiac-muscle patches over an area of dead heart muscle in order to reduce the pathology that often leads to heart failure.

The research was led by Jianyi "Jay" Zhang, M.D., Ph.D., the chair of University of Alabama at Birmingham Biomedical Engineering, a joint department of the UAB School of Medicine and the UAB School of Engineering.

Each is 1.57 by 0.79 inches in size and nearly as thick as a dime. Zhang and colleagues found that transplanting two of these patches onto the infarcted area of a pig heart significantly improved function of the heart's left ventricle, the major pumping chamber. The patches also significantly reduced infarct size, which is the area of dead muscle; heart-muscle wall stress and heart-muscle enlargement; as well as significantly reducing apoptosis, or programmed cell death, in the scar boarder area around the dead heart muscle. Furthermore, the patches did not induce arrhythmia in the hearts, a serious complication observed in some past biomedical engineering approaches to treat heart attacks.

The dishes on the rocker are growing large, human cardiac-muscle patches. This rocking at 45 rpm during growth greatly improves the maturation of cardiomyocyte cells. Each patch, intended for transplantation to an infarcted heart, measures about 1.6 by 0.8 inches in size and is the thickness of a dime. Credit: UAB

A key to success of the patches is how they are engineered.

Each patch is a mixture of three cell types—4 million cardiomyocytes, or ; 2 million endothelial , which are well-known to help cardiomyocytes survive and function in a micro-environment; and 2 million , which line blood vessels. The three cell types were differentiated from cardiac-lineage, human induced , or hiPSCs, rather than using hiPSCs created from skin cells or other cell types.

Each patch was grown in a three-dimensional fibrin matrix that was rocked back and forth for a week. The cells begin to beat synchronously after one day.

This mixture of three and the dynamic rocking produced more heart muscle cells that were more mature, with superior heart-muscle physiological function and contractive force, as compared with patches made from a monolayer of cells that are not dynamically rocked. The patches resembled native heart-muscle tissue in their physiological and contractile properties.

To prepare large, human cardiac-muscle patches for transplantation to infarcted hearts, they were grown on a rocker for 7 days. At that time, the patches show spontaneous and synchronized contractions. Credit: UAB

Past attempts to use hiPSCs to treat animal models of heart attacks—using an injection of cells or cells grown as a very thin film—have shown very low rates of survival, or engraftment, by the hiPSCs. The present study had a relatively high rate of engraftment, 10.9 percent, four weeks after transplantation, and the transplantation led to improved heart recovery.

Part of the beneficial effects of the patches may occur through the release of tiny blebs called exosomes from cells in the patches. These exosomes, which carry proteins and RNA from one cell to another, are a common cell-to-cell signaling method that is incompletely understood. In tissue culture experiments, the researchers found that exosomes released from the large heart-muscle patches appeared to protect the survival of heart-muscle cells.

Additionally, the patches appeared to prevent or reverse detrimental changes in protein phosphorylation in the sarcomeres of the heart-muscle tissue bordering the infarcted area of the heart. This result is the first to suggest that hiPSC-derived heart cells may improve contractile function after heart attacks by lessening maladaptive changes in phosphorylation states of sarcomeric proteins. The sarcomere is the contractile unit in a heart-muscle cell myofibril.

Explore further: Tissue engineering advance reduces heart failure in model of heart attack

More information: Ling Gao et al, Large Cardiac-Muscle Patches Engineered from Human Induced-Pluripotent Stem-Cell-Derived Cardiac Cells Improve Recovery from Myocardial Infarction in Swine, Circulation (2017). DOI: 10.1161/CIRCULATIONAHA.117.030785

Related Stories

Tissue engineering advance reduces heart failure in model of heart attack

January 26, 2017
Researchers have grown heart tissue by seeding a mix of human cells onto a 1-micron-resolution scaffold made with a 3-D printer. The cells organized themselves in the scaffold to create engineered heart tissue that beats ...

Saving hearts after heart attacks: Overexpression of a gene enhances repair of dead muscle

October 17, 2017
University of Alabama at Birmingham biomedical engineers report a significant advance in efforts to repair a damaged heart after a heart attack, using grafted heart-muscle cells to create a repair patch. The key was overexpressing ...

Beating heart patch is large enough to repair the human heart

November 28, 2017
Biomedical engineers at Duke University have created a fully functioning artificial human heart muscle large enough to patch over damage typically seen in patients who have suffered a heart attack. The advance takes a major ...

3-D-printed patch can help mend a 'broken' heart

April 14, 2017
A team of biomedical engineering researchers, led by the University of Minnesota, has created a revolutionary 3D-bioprinted patch that can help heal scarred heart tissue after a heart attack. The discovery is a major step ...

Stem cell patch shows early promise in treating heart failure

April 5, 2017
Patching a damaged heart with a patient's own muscle stem cells improves symptoms of heart failure, according to a Phase I clinical trial reported in Journal of the American Heart Association, the Open Access Journal of the ...

Recommended for you

Obesity linked with higher chance of developing rapid, irregular heart rate

April 18, 2018
People with obesity are more likely to develop a rapid and irregular heart rate, called atrial fibrillation, which can lead to stroke, heart failure and other complications, according to Penn State researchers.

Comparing strategies to guide blood pressure treatment

April 18, 2018
A strategy that examines a patient's overall heart disease and stroke risk to determine blood pressure treatment—rather than blood pressure levels alone—is more effective at preventing events like heart attacks, strokes ...

Using AI to detect heart disease

April 17, 2018
Heart disease is the leading cause of death for both men and women, according to the Centers for Disease Control and Prevention (CDC). In the U.S., one in every four deaths is a result of heart disease, which includes a range ...

Antioxidant therapy may reduce cardiovascular risk of young women with type 1 diabetes

April 17, 2018
The high estrogen levels that typically afford younger women protection from cardiovascular disease appear to instead multiply their risk if they have type 1 diabetes, researchers say.

Regular nut intake linked to lower risk of heart rhythm irregularity (atrial fibrillation)

April 16, 2018
Eating several servings of nuts every week may help lower the risk of developing the heart rhythm irregularity, atrial fibrillation, also known as heart flutter, finds research published online in the journal Heart.

Drinking up to 3 cups of coffee per day may be safe, protective: study

April 16, 2018
Many clinicians advise patients with atrial or ventricular arrhythmias to avoid caffeinated beverages, but recent research has shown that coffee and tea are safe and can reduce the frequency of arrhythmias, according to a ...

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.