The protein patch led to the regeneration of new heart muscle cells - highlighted in green - in mice that suffered heart attack.
Image credit: UCSD
Prof. Pilar Ruiz-Lozano, of Stanford University, CA, and colleagues publish the details of their creation in the journal Nature.
During a heart attack, or myocardial infarction, heart muscle cells - knowns as cardiomyocytes - suffer damage and die due to lack of oxygen from reduced blood flow. In adult mammals, cardiomyocytes are unable to fully regenerate following heart attack, and as a result, the heart muscle forms scar tissue in an attempt to heal.
At present, there is no treatment to effectively reverse damage caused by heart attack - a condition that affects around 735,000 Americans every year. Depending on the severity, such damage may lead to further complications, including arrhythmias - abnormal heart rhythms - and heart failure.
In their study, Prof. Ruiz-Lozano and colleagues set out to develop a treatment that addresses the inability of cardiomyocytes to regenerate.
Past studies in zebrafish, whose heart cells have the ability to regenerate, have revealed that the epicardium - the inner layer of the pericardium, which lines the wall of the heart muscles - plays a role in the regeneration of cardiomyocytes.
"We wanted to know what in the epicardium stimulates the myocardium, the muscle of the heart, to regenerate," says Prof. Ruiz-Lozano.
Patch embedded with FSTL1 protein led to cardiomyocyte regeneration
By analyzing the epicardial cells of healthy mammalian hearts, the team found that these cells triggered replication of cardiomyocytes.
The team used mass spectrometry to analyze more than 300 proteins produced by epicardial cells, in an attempt to identify a single compound that may be responsible for cardiomyocyte regeneration.
- Someone in the US has a heart attack every 43 seconds
- Coronary artery disease is the primary cause of heart attack
- Of the 735,000 heart attacks that occur in the US each year, 525,000 are a first heart attack.
Applying high throughout technology to the shortlisted candidates, the team identified a natural protein called Follistatin-like 1 (FSTL1) in epicardial tissue that stimulates cardiomyocytes to replicate. The team found, however, that after a heart attack, this protein diminishes in the epicardium.
The team then came up with a novel idea to turn their findings into a therapeutic strategy for heart attack. They created a patch made of acellular collagen that simulates fetal epicardial tissue and is embedded with FSTL1. The patch and the FSTL1 protein is slowly absorbed when applied to a damaged heart.
On testing the patch on the hearts of pigs and mice that had been damaged by heart attack, the team found it began to trigger regeneration of existing heart muscle cells and growth of new blood vessels within 2-4 weeks. This improved the overall heart function of the animals, as well as their survival - even when the patch was applied a week after heart attack.
"Many [of the animals] were so sick prior to getting the patch that they would have been candidates for heart transplantation," notes Prof. Ruiz-Lozano.
Study co-author Mark Mercola, professor of bioengineering at UCSD, says the team is "excited" by the findings, stating that the patch is "clinically viable" and "clinically attractive." What is more, because the patch is acellular - meaning it contains no cells - a patient would not need to use immunosuppressive medication.
Prof. Ruiz-Lozano believes the findings pave the way for a "completely revolutionary" treatment for heart attack patients, and the team hopes the patch will enter human clinical trials within the next 2 years.
The authors conclude:
"The data suggest that the loss of epicardial FSTL1 is a maladaptive response to injury, and that its restoration would be an effective way to reverse myocardial death and remodeling following myocardial infarction in humans."
Medical News Today recently reported on new guidelines from the US Preventive Services Task Force (USPSTF) recommending that adults aged 50-59 take low-dose aspirin daily in order to prevent first heart attack or stroke.