Abstract 18758: Hypertrophy of Neonatal Cardiomyocytes in 3D Engineered Cardiac Tissue Induced by Activation of mTOR Signaling

Introduction: An in vitro system inducing robust hypertrophy of neonatal cardiomyocytes (CM) is highly useful for studying cardiac development and improving function of engineered cardiac tissues. Our objective was to establish a methodologically simple way to hypertrophy CMs in densely-packed engineered 3D tissues, and to identify signaling pathways involved. Hypothesis: We hypothesized that hypertrophy could be induced by enhancing mass transport of nutrients to CMs in degradable hydrogel, and this effect would act through mTOR signaling pathway. Methods: Neonatal rat CMs were embedded in fibrin-based hydrogel to form cardiac microbundles, which were cultured for 2 weeks on either a static or dynamic platform. Results: Dynamic culture increases the volume occupied by CMs (Fig 1A), quantified as 2.3-fold increase in CM cross-sectional area (Fig 1B). The amount of sarcomeric proteins was increased by 2.4 to 4.6 fold in dynamically cultured tissues (Fig 1C). mTOR phosphorylation was increased by 51% upon t...