Abstract P1074: In Vitro Stimulation-conduction Platforms To Mature Induced Pluripotent Stem Cell-derived Cardiomyocytes

Abstract

Figure 1. Scaffold (i) and bioreactor (ii) viability for iPSC-CM conduction-stimulation platform.Heart disease is the leading cause of death worldwide. Cardiac tissue engineering offers various solutions, frequently employing induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs). iPSC-CMs can be expanded limitlessly and used autologously; however, they are immature compared to healthy, adult cardiomyocytes in vivo . We are interested in conductive scaffolds to mature iPSC-CMs by facilitating gap-junctional coupling in the presence of electrical stimulation. We have previously endowed electrospun scaffolds with high conductivity by incorporating carbon nanotubes (CNTs). We differentiated iPSCs into iPSC-CMs with a Wnt inhibitor-directed protocol. We confirmed CNT scaffold biocompatibility by seeding iPSC-CMs onto scaffolds with and without CNTs; 24 hours later, a live/dead assay indicated scaffolds exhibited no cytotoxicity (Fig. 1i). We also confirmed that the application of voltage-controlled electrical stimulation (square wave, 5 ms period, 20% duty cycle) for 5 minutes at magnitudes of 0, 0.1, 1, and 10 V did not introduce cytotoxicity (Fig. 1ii). Furthermore, application of 0.1 V resulted in earlier ultrastructure development and beating. We have developed an upgraded bioreactor which we will use to probe the role of electrical signals in embryonic cardiac development and to explore the ability of CNT scaffolds to electrophysiologically mature iPSC-CMs in the presence of electrical pacing. If successful, this could pave the way for advances in cellular pacemaking, physiologically relevant models, and cardiac tissue regeneration.