Scientists Have 'Healed' a Heart Attack in Mice by Regenerating Muscle Cells

After a heart attack, scientists have created a novel approach that can mend and even regenerate heart muscle cells (or myocardial infarction).

Although it has only been tried on mice, if it works as well in humans, it might be a life-saving therapy for patients who have had a heart attack.

A synthesized messenger ribonucleic acid is used in this method (mRNA). The body uses the 'blueprint' of DNA sequences created by mRNA to generate the proteins that make and govern our cells. Scientists can provide various instructions for different biological processes by tinkering with mRNA.

The altered instructions stimulate heart muscle cell replication (cardiomyocyte replication) via two mutant transcription factors, Stemin and YAP5SA.

The goal is to make cardiac muscle cells, which have a limited ability to regenerate, function more like stem cells, which the body can transform into a variety of specialized cells.

"No one has been able to do this to this extent and we think it could become a possible treatment for humans," says University of Houston scientist Robert Schwartz.

Because just around 1% of adult cardiac muscle cells can regenerate – the cardiomyocytes we have when we die are essentially the same ones we had when we were born - heart attacks and heart disease can leave the heart permanently vulnerable.

Stemin was demonstrated to switch on stem cell-like qualities in cardiomyocytes in tissue culture dishes and in vivo mice, whereas YAP5SA enhanced organ development and replication. The club has referred to the procedure as a "game-changer."

Myocyte nuclei multiplying by at least 15-fold in the 24 hours following injections of the mutant transcription factors Stemin and YAP5SA, according to an in vivo study using living mice with injured hearts.

"When both transcription factors were injected into infarcted adult mouse hearts, the results were stunning," adds Schwartz.

"The lab found cardiac myocytes multiplied quickly within a day, while hearts over the next month were repaired to near normal cardiac pumping function with little scarring." 

The researchers claim that the synthetic mRNA supplied to the cells vanished after a few days, precisely as the mRNA created in human bodies. This provides the new method an edge over gene therapy procedures that are difficult to halt or delete once they've started.

Although it remains to be seen if the strategy can be effectively translated into people – and many more years of research will be necessary to turn this into a viable treatment – the research team is optimistic.

More research is being done to learn more about heart illness and cardiac damage, as well as how the body reacts in the aftermath. Scientists continue to focus on cardiovascular health, as heart disease is the leading cause of mortality in the United States (accounting for around a quarter of all deaths).

"This is a huge study in heart regeneration especially given the smart strategy of using mRNA to deliver Stemin and YAP5SA," adds University of Houston scientist Siyu Xiao.