Biochemists find a way to mend a broken heart

Novel technology returns cardiomyocytes to a stem cell-like state to promote their proliferation and regeneration in an in vitro study.

Researchers at the University of Houston (TX, USA) have developed a strategy to repair and regenerate heart muscle cells called cardiomyocytes. “No one has been able to do this to this extent and we think it could become a possible treatment for humans,” said Robert Schwartz, who leads the research group.

The researchers used synthetic messenger RNA (mRNA) to deliver two mutated transcription factors called STEMIN and YAP5SA to mouse hearts in an in vitro tissue culture study. They showed that these transcription factors work together to replicate cardiomyocytes. STEMIN triggers stem cell-like properties in the cardiomyocytes, while YAP5SA promotes organ growth causing the muscle cells to replicate.

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

The synthetic mRNA used to transport the transcription factors is it is broken down within a few days and offers a more controllable gene expression when compared with gene therapy that’s delivered using viral vectors, reducing biosafety concerns.

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This strategy was also used in a separate in vivo study in mice by the same research group. The researchers delivered these transcription factors and mRNA through injections into the damaged hearts of mice and found that the myocyte nuclei replicated at least 15-fold in 24 hours.

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

Regenerating heart muscle cells is especially important considering that less than 1% of adult cardiomyocytes can regenerate, meaning that most of our cardiomyocytes have been with us since the first month of our life. The contracting ability of the heart can be impacted following a heart attack when some of these cells die, so regenerating these cells could be a possible treatment following heart attacks or for other heart diseases.

Xiao concluded: “This is a huge study in heart regeneration especially given the smart strategy of using mRNA to deliver STEMIN and YAP5SA.”