Researchers at the University of Houston have demonstrated a new technique for helping heart cells regenerate after a heart attack, using mRNA to return the cells to a stem-cell-like state. Tests in mice showed drastic improvements to heart function a month after a heart attack.
Unlike most tissues in the body, heart cells have a limited ability to regenerate after injury. That’s a big part of why heart attacks are so deadly – afterwards, non-beating scar tissue forms instead, which can lead to further attacks and eventually heart failure.
In recent years, scientists have been investigating how to repair broken hearts by regenerating the cells, with some success seen using placental stem cells, reprogramming structural cells into ones that beat, or using stem cell messengers to induce the heart to self-repair. Others have identified transcription factors that can get heart cells to begin replicating again.
In the new study, the Houston researchers identified two other mutated transcription factors, known as Stemin and YAP5SA, that can increase the rate of replication of heart cells called cardiomyocytes. Tests in mouse cells cultured in lab dishes revealed that Stemin activates stem-cell-like properties in cardiomyocytes, while YAP5SA boosts the process by promoting organ growth.
These two transcription factors are delivered to the heart cells using synthetic mRNA. This technology, widely used in COVID-19 vaccines, works by instructing cell ribosomes to produce certain proteins – in this case, Stemin and YAP5SA.
In other tests, the team injected mRNA containing the transcription factors into the hearts of live mice after a heart attack. Within 24 hours, the replication of the animals’ heart cells had increased by at least 15 times, which significantly improved cardiac function.
"When both transcription factors were injected into infarcted adult mouse hearts, the results were stunning,” said Robert Schwartz, lead author of the studies. “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.”
As with any animal study, the results may not necessarily apply to humans, but the team says that this kind of gene therapy has the potential to eventually be used to treat heart disease in humans.
The research was published in two studies in The Journal of Cardiovascular Aging.
Source: University of Houston
