Cardiomyocytes are cardiac muscle cells. They are terminally differentiated and facilitate contractile forces (“beatings”) of the heart. Grown in vitro as a monolayer sheath, cardiomyocytes are connected by gap junction proteins that help synchronize contraction-relaxation cycles of the cardiomyocytes. Cardiomyocytes may be used in various in vitro or in vivo studies; transplantation into normal or diseased systems; cardiac toxicology studies; or cardiovascular developmental studies. Cardiomyocytes have a high mitochondrial density, which allows them to produce adenosine triphosphate (ATP) quickly, making them highly resistant to fatigue.

What are the hallmarks of mature human cardiomyocytes?
It is a somewhat controversial topic. There are several ways to define mature cardiomyocytes. We found a reference paper (Bedada et al., 2014) that shows the transition from human TNNI1 (ssTnl) to TNNI3 (cTnI) in a specific stoichiometric manner is a reliable hallmark of mature “adult” cardiomyocytes. Another notable hallmark is calcium storage, (otherwise known as calcium handling), via functional sarcoplasmic reticulum (SR) structures in the cell. Ca signaling controls excitation–contraction coupling (ECC) in heart muscle (Hwang et al., 2015). L-type calcium currents, caffeine-induced calcium transients, and calcium transport are conducted by sarcoplasmic reticulum’s Ca ATPase transporters/ion channels and Na/Ca Exchangers. The importance of calcium can’t be emphasized enough: Intracellular calcium binds to the troponin complex and activates myofilament contractions. For relaxation to occur, calcium must be removed from the cytoplasm. Thus, calcium is the key to electrical activation and contraction, and dysfunctional calcium handling is associated with contractile dysfunction, arrhythmia, and other heart diseases.

How can we distinguish between ventricular and atrial cardiomyocytes?
Ventricular cardiomyocytes and atrial cardiomyocytes originate from the distinct mesoderm subpopulations. In this paper (Lee et al., 2017) describes that atrial and ventricular mesoderm are distinguished by RALDH2 and CD235a expression patterns. Furthermore, the reference paper describes the finding that atrial cardiomyocytes are influenced by autocrine retinoic acid signaling (specifically, between day 3 to day 5 of the ALDH+ mesoderm lineage).

Which cardiomyocyte “type” is appropriate for stem cell therapy?
Scientists debate about this question. Many agree that atrial cardiomyocytes are the preferred choice. However, questions remain as to 1) how can stem cells derived cardiomyocytes get transplanted into the human heart; and 2) how long will it take for patient’s body to integrate the transplanted exogenous cardiomyocytes.

Until next time!