Non-invasive analysis of contractility during identical maturations revealed two phenotypes in ventricular but not in atrial iPSC-CM

Abstract

Patient-derived induced pluripotent stem cells (iPSC) can be differentiated into atrial and ventricular cardiomyocytes to allow for personalized drug screening. A hallmark of differentiation is the manifestation of spontaneous beating in a 2D cell culture. However, an outstanding observation is the high variability in this maturation process. We valued that contractile parameters change during differentiation serving as an indicator of maturation. Consequently, we recorded non-invasively spontaneous motion activity during differentiation of male iPSC towards iPSC-cardiomyocytes (iPSC-CM) to further analyze similar maturated iPSC-CM. Surprisingly, our results show that identical differentiations into ventricular iPSC-CM are variable with respect to contractile parameters resulting in two distinct subpopulations of ventricular-like cells. In contrast, differentiation into atrial iPSC-CM resulted in only one phenotype. We propose that the non-invasive and cost-effective recording of contractile activity during maturation using a smartphone device may help to reduce the variability in results frequently reported in studies on ventricular iPSC-CM.