‘Groundbreaking’ study regenerates and heals heart muscles in mice after heart attack

Over a month, mice hearts were repaired to ‘near normal cardiac pumping function with little scarring’, say scientists

Scientists have developed a new method to repair and regenerate cardiac muscles in mice following a heart attack, an advance that may lead to novel drugs for treating heart disease in humans.

The “groundbreaking findings” were described last week in the Journal of Cardiovascular Aging. The new technology uses synthetic genetic material messenger RNA to deliver proteins that control the conversion of DNA into RNA in mice hearts.

“No one has been able to do this to this extent and we think it could become a possible treatment for humans,” Robert Schwartz, a co-author of the study from the University of Houston in the US, said.

Scientists demonstrated in studies conducted in tissue culture dishes that two proteins – Stemin and YAP5SA – work in tandem to increase the replication of heart muscle cells, or cardiomyocytes, isolated from mice.

“What we are trying to do is dedifferentiate the cardiomyocyte into a more stem cell-like state so that they can regenerate and proliferate,” Siyu Xiao, another co-author, explained.

The protein molecule Stemin, researchers say, is a “game-changer” that could turn on the stem cell-like properties from cardiomyocytes.

Meanwhile, they say YAP5SA works by promoting organ growth that causes the muscle cells to replicate even more.

In another study published in the same journal, researchers report that Stemin and YAP5SA could work together and repair damaged mice hearts in tissue culture dishes.

The muscle cell nuclei, scientists say, replicated at least 15-fold in 24 hours following heart injections that delivered those transcription factors.

“When both transcription factors were injected into infarcted adult mouse hearts, the results were stunning,” Dr Schwartz said.

“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,” he added.

One advantage of using synthetic mRNA according to the researchers is that it disappears in a few days as opposed to viral delivery.

Compared to other gene therapies delivered via viral vectors that raise biosafety concerns, scientists say mRNA-based delivery turns over quickly and disappears.

The findings are especially significant since heart muscle cells largely do not regenerate over a person’s life span.

Researchers say people generally die with most of the same cardiomyocytes they initially had in the first month of birth, and when there is a heart attack and cardiac muscle cells die, the contracting ability of the heart can be lost.

With less than 1 per cent of adult cardiac muscle cells regenerating, they say the findings are “huge” in heart regeneration “especially given the smart strategy of using mRNA to deliver Stemin and YAP5SA”.