31 August 2009

The patch for the heart grew in the omentum

Peter Smirnov, Infox.ruCardiovascular diseases reliably retain the first place among the direct causes of death.

The undisputed leader can be considered a myocardial infarction, which leads to the destruction of muscle tissue and filling the defect with a non-functional scar. Smadar Cohen from Ben-Gurion University in the Negev suggested patching the hole with a "half-dead" patch.

The skeleton of algae was populated with muscle cells, after which the implant was kept in the rat's omentum for another week, germinating vessels in it.

Scar overtakes muscle

An atherosclerotic plaque, a detached blood clot or droplets of fat can cost lives – unlike the same brain, the "pools" of arteries feeding the heart almost do not overlap. So any obstacle in the way of blood flow will inevitably leave an entire region without oxygen and fuel. Unfortunately, muscle cells are not able to survive even a small starvation – after a few hours without oxygen, irreversible, and, most importantly, avalanche-like destruction of heart tissue begins.

Dying cells fall apart, leaving behind a set of enzymes, poisons and other non-healing debris. The situation is also aggravated by the "cleaners" coming to the rescue — cells of the immune system. By hundreds of thousands migrating to the lesion, they disrupt the work of the surviving muscle cells.

The heartache does not end there – when the inflammation stops, the race between the scar and the muscle begins. Although irrefutable evidence has been obtained recently that cardiomyocytes still divide during life, the rate of their renewal is absolutely not comparable to the same connective tissue from which ligaments, tendons and dense component of the skin are made. For example, in a healthy heart, only 45% of muscle cells change by the age of 50, while vessels and membranes are completely renewed in four years.

With damage, whether it is a heart attack or a through wound, this difference in speed is significantly aggravated and instead of a muscle, the defect is replaced by connective tissue – exactly the same scar as in the liver with cirrhosis, when hepatocytes die from alcohol, viruses or drugs.

The surviving cells have to make a lot of effort to ensure that the vital organ continues to perform its function in a constant rhythm. But sometimes this may not be enough – the scar is significantly inferior to the muscle tissue in its biomechanical properties, not to mention the complete inability to reduce or conduct a nerve impulse. The result is a gradual bulging of the ventricular wall, often ending in a rupture.

Stem cells in the fight against heart attackThere are different ways to treat this condition.

And, of course, stem cells, coupled with tissue engineering, were also needed here. One of the first ideas was to increase vascular growth, which would lead to improved nutrition. It was based on the fact that regular injections of vascular endothelial progenitor cells contributed to the improvement of objective indicators in more than one hundred volunteers. However, the average improvement was only 1%, so they did not introduce this rather expensive technique into clinical practice.

But as soon as scientists learned how to get cardiomyocytes from embryonic stem cells, the engineering idea went further – cells obtained from embryos began to be introduced into the defect area. But here, despite the more significant positive effect, ethical restrictions got in the way.

So in most severe cases, you have to use the old, but no less effective way – surgically strengthen the defect with ordinary stitches or mesh. Let the artificial material never begin to knock in time, but it will not allow the wall to bend and even more so to break.

Vessels for the heart were grown in the omentumCohen and co-authors of the publication in the Proceedings of the National Academy of Sciences followed a proven path, not forgetting about both of the technologies mentioned above.

They first populated a three—dimensional implant made of porous alginate with precursor cells of muscle tissue. After that, they faced the main problem in tissue engineering: how to grow vessels inside this structure?

If the nutrient medium in the Petri dish washes the living implant from all sides, then there will be no such ideal conditions in the body and after transplantation, the "inhabitants" of the central part of the sample are threatened with imminent extinction. Scientists have repeatedly tried to solve this problem by populating the structure not only with muscle, but also with endothelial cells. And the vessels did grow, but with blind endings, and after transplantation they immediately gave a "leak".

Having decided that modern technologies are not yet able to solve this problem, Cohen suggested using the resources of the body itself – before transplanting into the heart, the patch was sewn into the omentum located in the abdominal cavity for a week.

During this time, the artificial muscle cube did not swell with fat, but it was enriched with vessels so necessary for life.

A well - established patchAfter the heart transplant, the patch pleased the scientists even more.

Firstly, the wall maintained the required thickness during the entire observation period. Secondly, cardiomyocytes successfully integrated into the community – they began both to conduct electrical impulses and to contract. And this is a necessary condition that ensures the principle of "all-in", according to which the myocardium works. Unlike skeletal muscles, the heart has no nerves, so the muscle cells themselves have to spread excitement and they either contract all together or do not contract at all.

The functional abilities of the ventricle never reached the pre-infarction mark, although they came close to it. When transplanting a patch from the omentum, the heart missed only 5%, patches with vessels grown in a test tube – 13%, while tightening the edges of the defect with sutures led to a lag of 30%.

As for clinical implementation, it is not worth waiting for it in the near future, as is often the case with cellular technologies. And it's not the cost (Cohen could not do without fetal tissues), but the fact that scientists populated the patch with muscle cells isolated from rat embryos. But the idea of "growing up" the vessels in the omentum will certainly take root in tissue engineering. There is no better bioreactor for spare parts yet.

Portal "Eternal youth" http://vechnayamolodost.ru31.08.2009

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