New patches made with human cells help boost recovery from heart attack

A research has been conducted to enhance recovery from heart attack.

For the first time, large human cardiac-muscle patches have been tested in the lab on large animals in a heart attack model. It showed that it resulted in improved recovery from heart attack injury.

This is the first large-animal study of muscle patches carried with a goal of treating human heart attacks by suturing cardiac-muscle patches over a specific area of dead heart muscles. It was carried out in order to reduce the pathology that often leads to heart failure.

The research was conducted by Jianyi 'Jay' Zhang, from University of Alabama at Birmingham Biomedical Engineering, a joint department of the UAB School of Medicine and the UAB School of Engineering.

Each patch 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 infarct area of a pig heart significantly improved the 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 border 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.

A mixture of three cells - two million endothelial cells - known to help cardiomyocytes function and survive in a micro-environment, 2 million smooth muscle cells - known to line blood vessels, and 4 million cardiomyocytes - known as heart-muscle cells, each patch is grown in a 3-D fibrin matrix. Subsequently, it is rocked back and forth for a week and all cells start to beat synchronously after day one.

The three cell types are differentiated in the making from cardiac-lineage human-induced stem cells, also known as hiPSCs.

Dynamic rocking and the apt mixture produce more quantity of mature heart-muscles cells, with more contractive force and superior physiological function, as compared to patches made with mono-layered cells which are not dynamically rocked.

In the past, attempts to use hiPSCs to treat large animal models of heart attacks have shown very low rates of engraftment or survival. The current research shows a relatively higher rate of engraftment - 10.9 percent - after four weeks of transplant which resulted in improved heart recovery.

These patches also release tiny blebs called exosomes which carry RNA and proteins from one cell to other. In tissue culture experiments, it is found that such exosomes which are released from large heart-muscle patches help in the survival of heart-muscle cells.

Additionally, these patches are found to reverse or prevent detrimental changes in protein phosphorylation in the sarcomeres of heart-muscle tissues bordering the infarct of the heart. This result suggested that hiPSC-derived heart cells may improve contractile function after heart attacks.

The research was conducted by the University of Alabama at Birmingham.