Human Cardiac Fibroblast Number and Activation State Modulate Electromechanical Function of hiPSC-Cardiomyocytes in Engineered Myocardium

Figure 6

P9 hCFs reduce mechanical performance but maintain kinetic properties imparted by p4 hCFs after one week of culture. (a) Cross-sectional area (CSA) of tissues was measured at relaxed length. (b) Young’s Modulus was measured by stretching tissues from relaxed length to 130%. (c) Active stress was measured as the average peak contractile force of tissues paced at 1 Hz field stimulation. (d) Maximum capture rate of tissues was measured during pacing from 1 Hz to 4 Hz field stimulation. independent experiments, number of tissues tested is indicated on each bar, , and data are represented as . (e) Contractile stress normalized to maximum stress of control (hiPSC-cardiomyocyte-only) tissues as a function of engineered cardiac tissue (ECT) cardiomyocyte purity. Gaussian curves fitted to control and +p4 hCFs with dotted lines indicating 95% confidence interval. Each point represents results from an independent experiment (unique cardiomyocyte purity), with 2-6 tissues measured per group per experiment; data are represented as . (f–i) Tissue force amplitude and kinetics were measured as a function of increasing pacing frequency. Active stress (f), upstroke velocity (g), time to 50% relaxation from peak stress (T50 (h)), and time to 90% relaxation from peak stress (T90 (i)) are shown normalized to the value of a given experimental condition at 1 Hz. Width of bars represents relative amplitude, and color of bars represents the percentage of tissues following the pacing with 1 : 1 capture rate compared to 1 Hz. Bold numbers indicate the value of a respective metric in 5% p4 hCF tissues at 1 Hz pacing. independent experiments.