Circulating Immune Profile of Aging : a Translational Study on the Role of Growth Differentiation Factor-15 and Monokine induced by Interferon Gamma

The ability to use light to stimulate mammalian cells has significantly augmented our understanding of electrically excitable tissues in health and disease, paving the way toward various novel applications in the research and therapeutic fields. Here, we demonstrate full optogenetic control of human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CM). We simultaneously introduced channelrhodopsin-2 (ChR2) and a third-generation halorhodopsin (NpHR3) into hiPSC via a polycistronic lentiviral vector. Via directed differentiation, we created opsinexpressing cardiomyocytes. To quantify the impact of photostimulation on these cells, we assessed evoked electrical and mechanical signals. With the application of blue (470 nm) and yellow (580 nm) light, we show both activation and inhibition of cardiomyocyte contractions, respectively. To illustrate the utility of our system, we have synchronized our light-sensitive cardiomyocytes with discarded primary human heart tissue, in vitro. In addition, we have created threedimensional optogenetic engineered heart muscle (o-EHM) that can be activated and inhibited with light; this offers a way to immediately and orthogonally synchronize this muscle with native heart rhythms. Our system provides insight into whether hiPSC-CM have the potential to be synchronized to recipient hearts in vivo upon therapeutic delivery, either as individual cardiomyocytes or as a component of engineered muscle.