Two-compound mix pushed adult heart cells toward an embryonic-like state

Phenylephrine and harmine worked in sequence to activate cell-division programs in laboratory and in vivo experiments.

Editorial illustration — not from the study.

Researchers identified a two-compound treatment made from phenylephrine hydrochloride and harmine that increased the division of adult heart-muscle cells in laboratory and in vivo experiments. The treatment simplified an earlier five-compound mixture that had also been linked to heart-cell proliferation and regeneration.

The compounds acted in sequence. Phenylephrine activated an embryonic or fetal-like program and helped cells enter the first stages of division, while harmine activated genes needed for the later stages and completion of cell splitting.

How the two compounds worked

The researchers identified a dual-compound cocktail, called 2SM, made up of phenylephrine hydrochloride and harmine. It enhanced adult cardiomyocyte proliferation in vitro and in vivo, and analyses of gene activity and metabolism indicated that it activated cell-cycle programs and changed how the cells processed energy.

Phenylephrine activated a fetal program through the mTOR signaling pathway and increased CCND1 and WEE1, allowing cardiomyocytes to enter the G1/S phase of the cell cycle. Harmine inhibited DYRK1A and activated the MMB and FOXM1-MuvB complexes, increasing gene activity linked to the G2/M phase. Sequential treatment, with phenylephrine given before harmine, was necessary for the cells to complete cytokinesis, the final physical separation into two cells.

Overall, the researchers concluded that 2SM reprogrammed cardiomyocytes into an embryonic-like state and coordinated their progression through the cell cycle. The two-compound treatment was presented as a simpler version of an earlier five-compound cocktail.

Why the simpler mix matters

Adult mammalian heart-muscle cells normally have limited ability to regenerate, which makes recovery after a heart attack difficult. A simpler treatment that increases cardiomyocyte proliferation could make the underlying biology easier to study and may be more practical to investigate than the earlier five-compound mixture. However, the abstract describes experimental evidence rather than a tested treatment for people.

Evidence and open questions

This journal article reports findings from laboratory experiments on cardiomyocytes and in vivo experimental models. The abstract does not give sample sizes, identify the animal models, or report whether the treatment restored heart function after myocardial infarction. It also provides no evidence from human studies, so the findings do not establish whether the two-compound treatment is safe or effective as a therapy.

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