A team of researchers from the University of Houston (UH) is developing pioneering strategies to help regenerate heart muscle cell formation.
The human heart doesn’t regenerate and the number of heart muscle cells drops as a person grows older. Cells lost as a result of heart attacks or other injuries are slowly replaced by connective tissue and not by new muscle cells in a process called fibrosis, which decreases the heart’s pumping ability.
The team of physicians and developmental biologists believes that a big part of why cardiovascular disease is the leading cause of death in the U.S. is due to the inability of the human heart to effectively repair itself after injury. The team aims to change these statistics.
Key findings of their research project were published in the journal Proceedings of the National Academy of Sciences (PNAS), titled “miR-322/-503 cluster is expressed in the earliest cardiac progenitor cells and drives cardiomyocyte specification.”
“We have uncovered new regulators of heart formation,” Yu Liu, one of the study’s lead authors and an assistant professor of biochemistry at UH, said in a press release. “Compared to most others, these new regulators, which are a small RNA species called microRNAs, act early in the multistep heart formation process. They are easier to deliver into human bodies, and thus have a shorter path to clinical use.”
The team focused on learning how a heart is formed in embryos, and wanted to determine if the new microRNAs could convert an abundant cell type, called fibroblasts, into heart and muscles.
The team was able to identify nearly 140 microRNAs in the earliest ancestor cells of the heart. They then screened for the ones that were active in heart muscle cell formation. The miR-322/503 cluster emerged as the top finding in the two screenings, and became the basis for the team’s work.
MicroRNAs have re-emerged as a key player in gene regulation, even though they were once thought to be useless. Using mouse models, Liu and his team were able to track the process of heart muscle cell formation in a process that involved several screening steps.
Robert Schwartz, another author of the study and a Cullen Distinguished Professor of Biochemistry, is researching ways to make heart muscle cells from fibroblasts, now a broadly accepted strategy.
“We were the first in converting human fibroblasts into cardiomyocytes,” he said. “I expect these microRNA regulators to be potent, either acting alone or in combination with the existing agents we have.”
Schwartz is also collaborating with NASA to explore how the particular space environment can assist in the creation of heart muscle cells out of fibroblasts. The microRNAs found will be significant to his effort.
Liu said he is hopeful their work at UH translates into using microRNAs to treat human heart attacks and other heart problems within the next decade.