Hard-to-Regenerate Cardiomyocytes Restored with Lipid Signaling Molecules in Blood [Health LAB]

[Financial News] A technology has been developed to produce cardiomyocytes using lipid signaling molecules in the blood. More than 90% of the cells differentiated into cardiomyocytes, and their heartbeat was close to that of an adult heart. In animal experiments, the technology restored cardiac function and reduced scarring. It is expected to be used in evaluating new heart disease drugs and in regenerative medicine.
According to KRIBB on the 2nd, a research team led by Son Mi-young, a professor in charge of the life sciences major at the Korea University of Science and Technology (UST), and Dr. Lee Mi-ok, a professor of life sciences at UST, at KRIBB's Stem Cell Convergence Research Center, found that lipid signaling molecules in the blood are key signals that promote the differentiation and maturation of cardiomyocytes. Using this finding, the team developed a technology to produce high-quality cardiomyocytes with functional characteristics close to those of adult heart cells.
According to the research team, the heart, the vital organ that pumps blood throughout the body, has very limited regenerative capacity once damaged. At present, regenerated cardiomyocytes remain in an immature, 'baby cell' state. As a result, they cannot beat as forcefully and regularly as an adult heart, and differentiation efficiency varies widely among cell lines.
The team was inspired by the observation that stem cells developed effectively into cardiomyocytes when bovine serum was added. Among the various components in the serum, the researchers focused on sphingosine-1-phosphate (S1P), a bioactive lipid signaling molecule, and S1PR1, the receptor that recognizes it. When human pluripotent stem cells were treated with S1P or the selective S1PR1 agonist SEW2871, more than 90% differentiated into cardiomyocytes, while their maturity and functional characteristics also improved.
The cardiomyocytes produced in this way grew larger, like adult cardiomyocytes, and the sarcomeres that make the heart beat were arranged more densely. Their beating signals and electrical properties also became much more regular and powerful.
In contrast, stem cells in which the S1PR1 gene had been removed using the CRISPR-Cas9 gene-editing technology failed to differentiate properly into cardiomyocytes even after treatment with S1P. This scientifically demonstrated that S1P-S1PR1 signaling plays a key role in the differentiation and functional maturation of cardiomyocytes.
Furthermore, when mature cardiomyocytes produced using this technology were transplanted into animals with myocardial infarction, the team confirmed therapeutic effects. The treatment significantly restored the damaged heart's pumping function, markedly reduced fibrosis that stiffens the heart, and enabled the transplanted cells to engraft successfully in the heart tissue.
This study is significant because it overcame the low maturity and differentiation efficiency of conventional stem cell-derived cardiomyocytes and enabled the stable production of cells with functional characteristics close to those of an adult heart. The technology could serve as a next-generation platform for evaluating the effects of drugs on the heart under conditions more similar to those in humans during the early stages of drug development. It is also expected to make a major contribution to developing cell therapies for fatal heart diseases such as myocardial infarction.
The findings were published online on July 2 in Experimental & Molecular Medicine (IF 17.5).

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