Cells derived from human pluripotent stem cells (hPSC) have already provided possibilities for replacing certain animal tissue-based tests. In particular, hPSC-derived cardiomyocytes (CM) are providing an attractive opportunity for front-loading cardiac safety pharmacology and toxicology. These cardiomyocytes express most relevant ion channels and demonstrate beating and action potentials similar to primary cardiac cells. However, when compared with primary adult cardiomyocytes, hPSC-CMs until now have remained immature, based on their resting membrane potentials, action potential characteristics and an ill-defined ultra-structural organization.

There are now many laboratories and some commercial suppliers which can produce large numbers of these cardiomyocytes, and a new initiative (Comprehensive in vitro Proarrhythmia Assay (CiPA)) is a novel cardiac safety screening proposal, part of which will use hPSC-derived cardiomyocytes.

Until now, almost all laboratories producing hPSC-derived cardiomyocytes have used – have had to use – culture systems containing serum. Two disadvantages are that 1) the cells remain somewhat immature even after long periods of culture, and 2) undefined growth hormones and/or tissue factors in the serum can give these cardiomyocytes variable characteristics.

To solve these problems, Pluriomics has now developed novel cell culture systems, which are free of serum and other undefined components. These novel systems support efficient differentiation and maturation of cardiomyocytes. Cardiomyocytes generated and maintained in this new culture system show enhanced sarcomeric organization, a more negative membrane resting potential and increased upstroke velocities.

We conclude that this next generation of cell culture technologies allows the generation of cardiomyocyte cells which more closely resemble human primary cells. In particular the avoidance of serum enables long term assays, without commonly-encountered problems such as compound plasma protein binding.