Anti-infarction patch
Patch with artificial cells restored the heart after a heart attack
Alice Bakhareva, N+1
Scientists have created a patch to restore the heart after a myocardial infarction. Artificial stromal heart cells containing paracrine factors of living human cells were placed in the cell matrix from the myocardium of a pig.
A patch for a heart made of a pig's cell-free myocardial matrix (bottom right). Top right: a secret is isolated from the stroma of the human heart and enclosed in biodegradable microparticles, such artificial cells are placed inside the scaffold. Here and below are the drawings from the article by Huang et al.
The pad helped to restore tissues and improve heart function after artificially induced myocardial infarction in rats and pigs, did not cause rejection and was not toxic. Even after freezing for a month, the patch has not lost its properties. The study is published in the journal Science Translational Medicine (Huang et al., An off-the-shelf artificial cardiac patch improves cardiac repair after myocardial infarction in rats and pigs).
Coronary heart disease is one of the leading causes of death worldwide. After the disease, irreversible changes occur, for example, with myocardial infarction, necrosis (death) of the heart area develops. After a heart attack, the repair process begins, which often leads to arrhythmia and heart failure. Scientists are trying to influence this process and trigger the regeneration of cardiac tissue with the help of cell therapy: stromal heart cells, for example, secrete paracrine factors that affect damaged cardiomyocytes.
However, living cells are very vulnerable, before transplantation they need to be kept in special conditions so that they remain viable, so cell therapy is time-consuming and expensive. Transplanted cells are easily washed out due to active contractions of the heart, and the number of engrafted cells is usually small. What's left can attack the immune system if the transplant is not autologous. In addition, the mechanism of action of cell therapy is not completely clear, and undifferentiated cells can divide uncontrollably and turn into tumors.
Ke Huang from North Carolina State University and his colleagues have created a patch with synthetic stromal heart cells. To make artificial cells, a secret was isolated from the stroma of the human heart and placed in biodegradable microparticles of polylactic-co-glycolic acid. These capsules were implanted into a matrix from the cell-free matrix of the pig myocardium using vacuum filtration. The advantages of this model are that the cell-free patch is easy to store (can be frozen) and it does not cause rejection.
Freezing for different periods, up to 28 days, did not affect the ability of the lining to isolate factors and its mechanical characteristics. Both the artificial cells themselves and the whole patch (fresh or frozen) stimulated differentiation and reduced cell death of neonatal rat cardiomyocytes in culture compared to the control (p<0.05). Similar results were obtained on the culture of human cardiomyocyte precursors.
To test the properties of the patch in vivo, myocardial infarction was induced in rats by ligating the left descending branch of the coronary artery. An overlay with a diameter of five millimeters was attached to the damaged area or artificial myocardial cells were injected.
Cells that were not retained by the matrix were washed out of the myocardium, while the patch effectively delayed them. The foreign object did not attract T cells or macrophages and did not cause immune rejection. The heart of rats that had a patch ejected more blood, the size of the area necrotized during a heart attack became smaller, more viable tissues and capillaries appeared under the patch, and the thickness of the ventricular wall increased. The effect of the lining remained even after it was frozen.
Sections of the rat heart stained with hematoxylin and eosin. On the left is the control, in the middle is an empty scaffold overlay, on the right is an overlay with artificial cells. There is an overlay from the bottom of the dotted line, heart tissues affected by infarction from above. Inside the small dotted line on the right picture is a viable tissue.
Then the scientists tested the overlay on a model of myocardial infarction in pigs. The heart of these animals is anatomically similar to a human, so they are often used for preclinical tests. During open-heart surgery, the pigs were bandaged with the left descending branch of the coronary artery, and then an overlay with a diameter of 3.5 centimeters was placed on the damaged area. After seven days, the animals were euthanized for histological studies of the heart.
A week later, on an electrocardiogram in pigs with an overlay, the ST segment, which becomes domed in myocardial infarction, returned to normal, unlike control animals. The size of the damaged area in the myocardium with patches significantly decreased (p=0.0158). Compared with the result obtained 24 hours after surgery, on the seventh day the left ventricular ejection fraction and heart contractility were increased. The concentration of immune cells in the blood of pigs that had pads did not increase, which means there was no rejection reaction.
The concentration of alanine aminotransferase and aspartate aminotransferase in the blood was not increased in rats on the 21st day after surgery, and in pigs on the seventh day. This suggests that the pad did not disrupt the liver. The authors made the same conclusion about the kidneys by measuring the concentration of creatinine and blood urea nitrogen.
Stem cells are also used in the cell therapy of heart diseases. However, it turned out that they do not divide in the heart, and dead cells are just as effective as living ones. This means that their action is mediated by other factors, including the inflammatory process.
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