Study Involving Gene Editing Finds a Way to Fix Damaged Heart Tissue

Study Involving Gene Editing Finds a Way to Fix Damaged Heart Tissue

Researchers working to stop the number one killer in the country have figured out why heart attack damage repair trials involving cell transplants end up failing and leading to fatal arrhythmias.

A study published in the Cell Stem Cell journal opens the door for a potential remedy, moving medicine one step closer to the objective of repairing the human heart.

University Health Network senior scientist Michael Laflamme, who was not directly involved in the research, says that “I don’t think this is science fiction that’s decades or centuries away. It’s happening already.”

Laflamme also praised the scientist team behind the study for managing to find a “viable path” that brings us closer to overcoming irregular heartbeats and the danger they pose.

That said path employs cutting edge editing as to replace the dead cells with brand new ones, reducing arrhythmias as a result.

According to Charles Murry, the study’s lead author, the heart loses about a quarter of its four billion cells during a typical attack.

Even if we’re lucky enough to survive a heart attack, our biology still works against us.

At birth, the human heart has the ability to regenerate, but for unknown reasons, it quickly loses that ability.

Instead, it substitutes dead tissue with a rigid scar that makes pumping blood more challenging.

Murry noted that oxygen flow to the heart slows down as a result, causing a rather deadly cycle that ends when “the heart can’t adapt to meet the circulatory demands of one’s body.”

Millions of cardiomyocytes, which are heart muscle cells with 4 altered genes, were implanted into minipigs by the University of Washington research team.

The MEDUSA cells adhered to the pig heart, coordinated their beat with neighboring cells, and reduced arrhythmias by 95 percent.

When arrhythmias did happen, they passed much more quickly.

Cell transplantation has long been investigated as a potential treatment for cardiovascular disease, which is responsible for one in every five deaths.

“My mother died of heart disease. I use as a benchmark, ‘Would I have put them in my mother?’ Knowing how they perform in pig hearts, yes.” Murry also said.

Cardiomyocyte injections result in arrhythmias, the team found, because the immature cells can’t sync with the heart’s electrical system, pushing the heart to beat way too fast.

Stem cells, which can develop into any of the two hundred cell types in the human body, were the scientists’ starting point for addressing these shortcomings.

In order to identify the genes most likely to contribute to the arrhythmias, they ran several trials.

In stem cells they changed various combinations.

The combinations were put to the test to see which resulted in the least amount of irregular heartbeats.

Arrhythmias were reduced but not completely by taking away 3 genes and adding 1.

Wolfram-Hubertus Zimmermann stated that “It’s an important contribution to have identified the culprit in the arrhythmias. It is clearly notable the previously observed massive arrhythmias weren’t seen, but the problem isn’t fully solved yet.”

Researchers have already started clinical studies of several cell therapies targeted at mending cardiac disease at Stanford Hospital in Palo Alto, California, as well as in Germany, Japan, and China.

Some entail injecting cardiomyocytes into the heart wall, while others call for sewing up cell-based patches to the heart.

The fact that cardiac muscle cells might be injected instead of open heart surgery is the procedure’s key benefit. 

According to Nenad Bursac, a professor of biomedical engineering whose lab has extensively used patches, the key benefit of the patches is that more of the transplanted cells manage to survive.

Because they’re detached and unable to get survival signals from surrounding cells, injected cells perish more quickly.

In addition, the cells in the heart’s wall do not initially have a blood supply that will provide oxygen to them.

Additionally, none of the five pigs that had MEDUSA cells implanted had suffered heart attacks.

As a result, the cells were less likely to result in irregular heartbeats and weren’t necessary for tissue repair.

Additionally, some scientists who were not involved in the study expressed concern that excessive gene editing in heart cells runs the risk of causing cancer or interfering with the essential tasks the cells carry out.

Silvia Marchiano, who was involved in the project for years, said that “Because we went through all these gene edits, the question we are now answering is just: ‘What if we compromised the cells too much?'”

He went on to add that one of the genes SLC8A1, out in MEDUSA cells, is able to “impact the ability of heart cells to contract. I think that the concept of editing these genes is powerful. Maybe a simpler combination may work.”

According to Kamp, the ideal approach would entail creating a line of cells that could be purchased over-the-counter and utilized by a variety of patients without having them to take immune suppressant medicines.

The drugs are required to prevent the immune system from attacking injected cells because it thinks they’re alien.

The director of the Stanford Cardiovascular Institute, Joseph Wu, states that “The arrhythmias are one of the key roadblocks. The investigators conducted a crucial study but will need to test more animals to show these genetically modified cells don’t cause irregular rhythms and can improve heart function.”

9 to 18 heart attack patients will participate in Wu’s clinical experiment, in which cardiac muscle cells that Wu has generated from stem cells without undergoing gene editing will be injected through a catheter.

To stop the potentially fatal arrhythmias, patients will also be given medication.

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