Regenerating Heart Muscle Cells with mRNA

Heart failure’s underlying cause is the loss of cardiomyocytes, which is a major cause of mortality and morbidity in the elderly. In addition, aging is associated with loss of sarcomeres and cardiac myocyte dysfunction. Normal repair processes are inadequate to deal with extensive myocardial damage.

Heart transplantation is the standard for treatment, but the limited availability of donor hearts and the risk of rejection restrict its use. 

Recently, researchers at the University of Houston reported a first-of-its-kind technology that has the ability to not only repair but also regenerate heart muscle cells following a myocardial infarction. The study was recently published in the Journal of Cardiovascular Aging. 

Transcription Factors able to Increase Heart Cells Replication

For the study, the team hypothesized that disruption of interactions of Serum response factor (SRF) with NKX2-5 and GATA4 would lead to dedifferentiation of cardiomyocytes to a proliferative stem cell state. SRF is a transcription factor that plays a key role in the transduction of mechanical signals from actin in the cytoplasm and the extracellular environment, to the nucleus. 

The technology developed by the team uses synthetic messenger ribonucleic acid (mRNA) to deliver mutated transcription factors to mouse hearts. They demonstrated that 2 transcription factors, Stemin and YAP5SA, work together to increase the replication of cardiomyocytes. 

Stemin turns on stem cell-like properties from cardiomyocytes, and YAP5SA works by promoting organ growth that increases myocyte replication. 

In another study, the same team will report that both transcription factors caused a 15-fold increase in replication in 24 hours following heart injections in mice. 

Another fantastic finding was that not only did myocytes replicate quickly within a day, but also were repaired to near normal cardiac pumping function within a month. 

Sources:

University of Houston. “Biochemistry researchers repair and regenerate heart muscle cells: Discovery has potential to become ‘powerful clinical strategy’ for treating heart disease.” ScienceDaily. ScienceDaily, 16 June 2022.
<www.sciencedaily.com/releases/2022/06/220616142756.htm>. 

Siyu Xiao, Rui Liang, Azeez B. Muili, Xuanye Cao, Stephen Navran, Robert J. Schwartz, Dinakar Iyer. Mutant SRF and YAP synthetic modified mRNAs drive cardiomyocyte nuclear replication. The Journal of Cardiovascular Aging, 2022; 2 (3): 29 DOI: 10.20517/jca.2022.17 

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