The buildup of scar tissue that slowly leads to heart failure could be reduced and replaced by health heart muscle using a method developed by researchers at the University of North Carolina School of Medicine.
The treatment could come in the form of a pill, and could lead to significantly improved quality of life for heart patients.
“Our past work brought hope that we could one day improve heart function in people with heart failure by converting scar tissue into beating heart muscle,” said Li Qian, PhD, assistant professor of pathology and laboratory medicine and senior author of a new study.
“But that was more of a proof-of-principle study, and the conversion rate was quite low. Now we have found the barrier to conversion, and by removing it, we have been able to significantly increase the yield of muscle-like cells.”
The “past work” refers to a 2012 study in which Qian and her colleagues created a blend of proteins to converted fibroblasts, which create scar tissue, into cardiomyocytes – heart muscle cells that beat on their own just as regular heart muscle cells do.
The approach lowered the likelihood of uncontrolled cell growth and tumor formation, shrinking the size of scar tissue and improving heart function in experiments on mice.
Getting quicker results
However, the new study has dealt with how slowly improvements came with the 2012 method.
“We wanted to have a better yield and shorten the conversion time so in the future this process could be fast, easy, and efficient for disease modeling or for treatment,” Qian said.
Their chance came with they discovered that a gene called Bmi1 interfered with the expression of other key genes needed to convert fibroblasts into heart muscle cells.
When the team depleted Bmi1, the percentage of fibroblasts that transformed into heart muscle cells increased 10-fold. This development also allowed for a simpler cocktail of proteins.
Ultimately, that cocktail could be put into a pill that could be given to heart patients, reducing the long-term loss of functional heart tissue.
The next step is to test the method on larger animals, which if successful could lead to a pill within 10 years.
Heart failure affects an estimated 5.7 million people in the United States, but currently has no cure, and treatment involves piecemeal methods that are cobbled together.
Symptoms including shortness of breath, fatigue, and swelling all worsen over time as a heart weakens.
“Our hope is that this approach could extend the lives of people with heart failure and markedly improve their quality of life in the future,” said Qian, who is also a member of the McAllister Heart Institute at UNC.
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