A new therapy that can induce heart cells to regenerate after a heart attack

via King’s College London

Researchers from King’s have found that therapy that can induce heart cells to regenerate after a heart attack.

Myocardial infarction, more commonly known as a heart attack, caused by the sudden blocking of one of the cardiac coronary arteries, is the main cause of heart failure, a condition that now affects over 23 million population in the world, according to the World Health Organisation.

At present, when a patient survives a heart attack, they are left with permanent structural damage to their heart through the formation of a scar, which can lead to heart failure in the future. In contrast to fish and salamander, which can regenerate the heart throughout life.

In this study, published today in Nature, the team of investigators delivered a small piece of genetic material, called microRNA-199, to the heart of pigs, after a myocardial infarction which resulted in the almost complete recovery of cardiac function at one month later.

Lead author Professor Mauro Giacca from King’s said: “It is a very exciting moment for the field. After so many unsuccessful attempts at regenerating the heart using stem cells, which all have failed so far, for the first time we see real cardiac repair in a large animal.”

This is the first demonstration that cardiac regeneration can be achieved by administering an effective genetic drug that stimulates cardiac regeneration in a large animal, with heart anatomy and physiology like that of humans.

“It will take some time before we can proceed to clinical trials,” said Professor Giacca.

“We still need to learn how to administer the RNA as a synthetic molecule in large animals and then in patients, but we already know this works well in mice.”

Professor Ajay Shah, British Heart Foundation (BHF) Chair of Cardiology and Head of the School of Cardiovascular Medicine and Sciences at King’s said: “A treatment that helps the heart repair itself after a heart attack is the holy grail for cardiologists. Professor Giacca’s study convincingly demonstrates for the first time that this might actually be feasible and not just a pipe-dream.

“It’s a very exciting advance in the field. While we are not yet at a stage where a treatment could be offered to patients, I’m confident that our excellent team in the King’s BHF Centre of Excellence is very well placed to drive forward the research to make such a treatment a reality.”

Learn more: Genetic therapy heals damage caused by heart attack

 

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Zebrafish could help mammalian hearts regenerate

via YourGenome.org

via YourGenome.org

Pitt researcher uses zebrafish to help mammalian hearts regenerate, including promising results in human heart cells in vitro

Many lower forms of life on earth exhibit an extraordinary ability to regenerate tissue, limbs, and even organs—a skill that is lost among humans and other mammals. Now, a University of Pittsburgh researcher has used the components of the cellular “scaffolding” of a zebrafish to regenerate heart tissues in mammals, specifically mice, as well as exhibiting promising results in human heart cells in vitro.

The findings offer promise to overcoming heart disease, the leading cause of death for men and women.

The study, led by Yadong Wang, the William Kepler Whiteford Professor in Bioengineering in the Swanson School of Engineering and the principal investigator of the Biomaterials Foundry at Pitt, found that a single administration of extracellular matrices (ECM) from zebrafish hearts restored the function of the heart and regenerated adult mouse heart tissues after acute myocardial infarction.

“The heart beats as if nothing has happened to it,” said Wang. “And our approach is really simple.”

The study also found that the zebrafish ECM protected human cardiac myocytes—specialized cells that form heart muscle—from stresses.

ECM are the architectural foundations of tissues and organs; not only do they provide a “scaffolding” on which cells can grow and migrate, they assist in the signaling necessary for the organ to develop, grow, or regenerate.

In mammals, the heart quickly loses the ability to regenerate after the organism is born, except for a brief period after birth. In lower animals, such as zebrafish, the heart retains that ability throughout their lives: up to 20 percent of a zebrafish’s heart can be damaged or removed, and within days the heart’s capacity has been fully restored.

Wang and his team first separated the ECM from the cells so that the recipient heart would not reject the treatment. They did this by freezing the zebrafish cardiac tissue, causing the cell membranes to burst and allowing the researchers to retrieve the ECM, a process called decellularization. Wang noted that he and his colleagues are among the first to decellularize non-mammalian tissues for applications in regenerative medicine. They then injected the ECM into the hearts of mice with damaged heart muscles and watched the hearts repair themselves.

“It’s difficult to inject foreign cells into a body because the body will recognize them as foreign and reject them; that’s not the case with ECM,” said Wang. Wang explained that, because ECMs are composed of collagen, elastin, carbohydrates and signaling molecules and have no cell surface markers, DNA or RNA from the donor, the recipient is less likely to reject the treatment.

Wang said that restored function starts almost immediately, and healing is noticeable as early as five days after treatment; within a week, his team could see the heart beating more strongly than the hearts of the untreated animals.

The researchers tested the effectiveness of ECM from normal zebrafish and from zebrafish with damaged hearts, in which the ECM had already begun the healing process. They found that while both types of ECM were effective in repairing damage to the mice hearts, the ECM obtained from the zebrafish hearts that were healing were even more potent in restoring heart function in the mice.

Wang is now working on a process to regenerate nerves in mammals using the same process and hopes to expand the heart treatments to larger animals in a future study.

Learn more: How Do You Mend a Broken Heart?

 

 

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