New technique helps injured hearts regenerate via stem cells

April 23 (UPI) — Engineers have developed a new way to help injured hearts regenerate using cells derived from human stem cells, potentially leading to better treatments for cardiac medical conditions.

Researchers at the Columbia School of Engineering and Applied Science found a way to treat the heart without implanting the cells, because in the past they didn’t work well with the heart and can cause abnormal heart rhythm. Instead they applied extracellular vesicles — a small structure within a cell — secreted by cardiomyocytes, which make up the cardiac muscle cells.

Their findings were published Monday in the journal Nature Biomedical Engineering.

“We reasoned that the cardiomyocytes would be the best source of molecules driving the recovery of injured heart, as it is well known that these cells can build muscle when used in tissue-engineering models,” co-leader author Bohao Liu, a medical and engineerring doctorate candidate in Columbia Engineering’s department of biomedical engineering, said in a press release. “I’m very excited about our promising results, and I believe that the cell-free therapy represents a step in the right direction for developing safe and effective treatments of the infarcted heart.”

Heart disease is the leading cause of death in the United States, killing more than 600,000 people each year, according to the Centers for Disease Control and Prevention.

When cardiomyocytes die, it irreversibly weakens the heart and limits its ability to pump blood. The heart is unable to regenerate itself.

With the new technique, cardiomyocytes from human pluripotent stem cells via a small sample of blood, leading to safer and more effective treatment of damaged hearts, the researchers found.

These cell-secreted microvesicles can be isolated, frozen and stored over long periods of time, the researchers report.

Although most of the implant cells are washed away within hours of the treatment, benefits were still seen. Researchers had a “hit-and-run” hypothesis, meaning the regulatory molecules could be delivered before leaving the injured portion of the heart.

“Consistent with this hypothesis, we postulated that the benefits of cell therapy of the heart could be coming from the secreted bioactive molecules [such as micro RNAs], rather than the cells themselves,” said Gordana Vunjak-Novakovic, a professor of medicine at Columbia University’s College of Physicians and Surgeons. “So we explored whether the benefits of cell therapy of the injured heart could be achieved without using the cells. This way, we would largely simplify the translation into the clinic, and avoid the burden of arrhythmia associated with implantation of contractile cells.”

These cells contain genetic messages that can communicate with recipient cells, she said.

The team of bioengineers, clinicians and systems biology scientists took cardiomyocytes from adult human stem cells and placed them in culture to allow them to secrete extracellular vesicles.

They found that the extracellular vesicles from cardiomyocytes contained cardiogenic and vasculogenic microRNAs but not from stem cells.

The team then enclosed the vesicles in a collagen-based patch that slowly released them over four weeks when implanted onto the injured heart of rats after a heart attack.

“We were really excited to find that not only did the hearts treated with cardiomyocyte extracellular vesicles experience much fewer arrhythmias, but they also recovered cardiac function most effectively and most completely,” Vunjak-Novakovic said. “In fact, by four weeks after treatment, the hearts treated with extracellular vesicles had similar cardiac function as those that were never injured.”

Next, the researchers plan to determine the optimal level of maturity of cardiomyocytes to maximize treatment outcomes.

“Once we better understand how exactly the extracellular vesicles do what they do, we should be able to extend their use to a range of cardiovascular diseases, and significantly advance the field of cell-free heart therapy,” Vunjak-Novakovic said.

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