Patches for the heart are being improved
Scientists grow heart cells in the laboratory
A section of heart muscle and other cells grown in the laboratory can help in recovery after a heart attack, – writes sciencemag.org .
Every 40 seconds, someone in the United States has a heart attack, in which up to a billion heart muscle cells suffocate. These lost cells never recover, leaving nearly 800,000 people a year disabled for life if they manage to survive.
Over the past 20 years, Nenad Bursak, a bioengineer at Duke University in Durham, North Carolina, has developed a "patch" that could replace cells destroyed by a heart attack. He found that in rodents, this "patch" can connect to the circulatory system and contract. The Bursak patch is now large and quite complex: the size of a poker chip (about 40 mm – VM) and the thickness of a sheet of cardboard – it can be tested on large animals," the scientist said at the Experimental Biology 2019 meeting in Orlando (Florida).
Holes along the edges of the "patch" of lab-grown human heart tissue (left) make it easier to attach it to the damaged heart. The enlarged image of the patch on the mouse heart shows capillaries (red) feeding muscle cells (green) – VM.
Like other researchers trying to repair damaged heart cells, Bursak starts with stem cells that can develop into specialized tissues such as heart muscle. But while some researchers inject hundreds of millions of individual heart muscle cells into the body, Bursak's team and several other groups grow into full-fledged pieces of heart muscle that surgeons can attach to the damaged heart. "This could be a transformational approach," says Ralph Marcusio, a developmental biologist at the School of Medicine at the University of California (San Francisco). Bursak's research "is the best in the field," adds Martin Dannwald, a cell biologist at the University of Iowa in Iowa City.
At some point, cardiologists decided that there was a secret supply of stem cells in the heart that could be stimulated for the natural restoration of the organ, but now most biologists agree that such cells do not exist in the heart. An alternative in early clinical trials is to make heart muscle cells in the laboratory from other stem cells, inject them into the artery supplying the heart, and hope that they settle in the organ and compensate for any dead tissue.
Bursak is skeptical about this approach, because the percentage of cells that survive after injection and enter the heart is very small. His approach requires open-heart surgery, but it provides a recovery method that more accurately takes into account the cell type and architecture of the real organ.
Bursak started this research as a graduate student. In laboratory conditions, he turned neonatal rat cells into heart muscle cells capable of contracting – this was the first time it was possible to do for mammals. Other researchers have developed tiny samples of heart tissue to test drugs in the laboratory. But Bursak wanted to fix the hearts directly. Over the years, his team has learned that the best scaffolds for stem cell cultivation are obtained from fibrin, a protein that helps form blood clots, and the best way to grow these scaffold cells is to gently swing them inside a suspended frame that allows the growing patch to move back and forth in a liquid medium. "These cells mature and are able to contract strongly," says Bursak.
In 2016, when his lab figured out how to produce these powerful contractions, the cardiac "patches" were tiny. Then, 2 years ago, the team grew a piece of heart muscle measuring 4 by 4 cm – potentially large enough to repair a damaged human heart.
"The size is impressive," says Christopher Chen, a bioengineer at Boston University. "It suggests that you can reach a scale that is clinically relevant."
Bursak's team also showed in rodents that the blood vessels of the heart can grow into a patch to keep it alive. Recently, scientists have also added to the "patch" populations of endothelial cells that develop into blood vessels, and fibroblast cells that help in its formation and strengthening. According to Bursak, so far the optimal ratio of cells in the patch is 70% of the heart muscle cells and 30% of the other two types of cells.
Researchers have already realized that when the patch is implanted in rats and mice, its capillary network connects to the rodent circulatory system. However, scientists do not yet know whether this will help the long-term preservation of an artificially created muscle area.
It is also not clear whether and how the patch will be electrically and mechanically integrated with the original heart so that they function as an integral unit. The "patch" will be sewn to the outside of the damaged heart, above the scar tissue, which makes it difficult to develop muscle coordination.
Perhaps scientists will be able to find the answer by conducting tests on pigs or other large animals.
There are also concerns about the use of the new method. Michelle Tallquist is a cardiovascular biologist at Hawaii State Medical University. John A. Burns in Honolulu is concerned that making a patch for a person who has suffered a heart attack may take too long – up to 6 months if the patient's own heart cells are used as a starting point.
According to Bursak, this can be avoided by creating a bank of immunologically selected stem cells, which can be implanted into an artificial "patch" in just 3 weeks, if necessary.
Perhaps soon scientists will be able to replace dead heart cells with living ones capable of beating and contracting.
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