Researchers at the University of Houston are reporting a first-of-its-kind technique that not only repairs heart muscle cells in mice, but also regenerates them after a heart attack or myocardial infarction, as shown in clinical trials. is well known.
Posted in Journal of Cardiovascular AgingThe unprecedented discovery has the potential to become a powerful clinical strategy for treating heart disease in humans, according to Robert Schwartz, Hugh Roy and Lily Kranz Cullen, Distinguished Professor of Biology and Biochemistry in the UH College of Natural Sciences and Mathematics. Is.
The new technique developed by the team of researchers uses the synthetic messenger ribonucleic acid (mRNA) to deliver mutated transcription factors — proteins that control the conversion of DNA to RNA — to the mouse heart.
“Nobody has been able to do this to such an extent and we think it could become a potential cure for humans,” said Schwartz, who has recently studied PhD graduate Siu Xiao and Dinkar, a research assistant professor of biology. Iyer led the study. and biochemistry.
Synthetic mRNA contributes to stem cell-like growth
The researchers showed that two mutated transcription factors, stemin and YAP5SA, work together to enhance the replication of cardiomyocytes, or heart muscle cells, isolated from mouse hearts. These experiments were performed in vitro on tissue culture dishes.
“What we’re trying to do is isolate the cardiomyocytes in a more stem cell-like state so they can reproduce and proliferate,” Xiao said.
Stemin turns on stem cell-like properties from cardiomyocytes. The important role of stamin in their experiments was discovered by Iyer, who said the transcription factor was a “game changer”. Meanwhile, YAP5SA works by promoting organ development that causes myocytes to replicate even more.
In a separate finding published in the same journal, the team will report that Stemin and YAP5SA repair damaged mouse hearts in vivo. Notably, myocyte nuclei replicated at least 15-fold in the 24 hours following cardiac injection that delivered those transcription factors.
Bradley McConnell, professor of pharmacology in the UH College of Pharmacy, and graduate student Emilio Lucero collaborated on the study by creating an infected adult mouse model.
“When both transcription factors were injected into infected adult mouse hearts, the results were surprising,” Schwartz said. “The lab found that cardiac myocytes multiply quickly within a day, while hearts are repaired with normal cardiac pumping function over the next month, with little scarring.”
An additional advantage of using synthetic mRNA, according to Xiao, is that it disappears in a few days, unlike viral delivery. Gene therapy delivered to cells by viral vectors raises several biosafety concerns as they cannot be easily prevented. On the other hand, mRNA-based delivery changes quickly and disappears.
limited number of cardiomyocytes
Schwartz and Iyer worked on this study for many years, and Xiao focused on this research during his doctoral studies at UH. She graduated in the fall of 2020.
“I feel honored and fortunate to have worked on this,” Xiao said. “This is a huge study in cardiac regeneration, especially given the smart strategy of using mRNA to deliver stemin and YAP5SA.”
The findings are particularly important because less than 1% of adult heart muscle cells can regenerate. “Most people die with the same cardiomyocytes they had in the first month of life,” she said. When a heart attack occurs and the heart muscle cells die, the contractile ability of the heart may cease.
The study was funded through a sponsored research agreement from the University of Houston, a Cullen-Ended Chair, the Texas Higher Education Coordinating Board, the Leduc Foundation, and Animatus Biosciences, LLC.
Other study contributors include Rui Lang from UH; and Zishi Chen and Jiang Chang from the Texas A&M Institute of Biosciences and Technology.
material provided by University of Houston, Original written by Rebecca Trejo. Note: Content can be edited for style and length.