US researchers have revealed a revolutionary method that not only regenerates but also repairs damaged cardiac muscle cells in mice.
No one has been able to do this to this level, and according to the study’s chief author, Robert Schwartz, “we think it may become a practical therapeutic for people.”
Schwartz has this distinction as a professor of biology and biochemistry at the University of Houston’s Hugh Roy and Lillie Cranz Cullen College of Natural Sciences and Mathematics.
He was accompanied by Dinakar Iyer, an associate professor of biology and biochemistry, and Siyu Xiao, a recent Ph.D. alumnus.
Stemin and YAP5SA
The researchers demonstrated that two mutant transcription factors, Stemin and YAP5SA, collaborate to increase the replication of cardiomyocytes, or heart muscle cells, isolated from mouse hearts.
There have been a number of in vitro experiments performed using tissue culture dishes.
“What we are trying to do is dedifferentiate the cardiomyocyte into a more stem cell-like situation,” Xiao said, “so that the cardiomyocyte can regenerate and multiply.”
Stemming activates the stem cell-like properties of cardiomyocytes.
Iyer recognized Stemin’s substantial contribution to their research, calling the transcription factor a “game changer.”
The myocytes continue to grow as YAP5SA encourages organ development, which causes them to do so even more.
Stunning results
Bradley McConnell, a professor of pharmacology at the University of Houston, and Emilio Lucero worked together to develop the infarcted adult mouse model used in the study.
When both transcription factors were injected into infarcted adult mouse hearts, the outcomes were “stunning,” according to Schwartz.
Over the course of the next month, hearts were restored to virtually normal cardiac pumping function without scarring, as determined by the laboratory.
According to Xiao, synthetic mRNA has an additional benefit over viral delivery in that it disappears in a few of days.
Gene therapies delivered to cells by viral vectors raise a variety of biosafety concerns since they cannot be easily halted. However, mRNA-based delivery rapidly deteriorates and disappears.
An extensive research
While Schwartz and Iyer worked on it for many years, Xiao focused on it throughout her Ph.D. studies at UH. In the fall of 2020, she will graduate.
Xiao continued, “I feel fortunate and blessed to have worked on this.” This is a significant research project in heart regeneration because of the ingenious usage of mRNA to transport Stemin and YAP5SA. Less than 1% of adult heart muscle cells can recover, making the discoveries all the more important.
She said that after a person went away, the bulk of their cardiomyocytes was still present. When heart muscle cells die during a cardiac attack, the heart’s ability to contract may be lost.
