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

Figure 3

Mechanical and kinetic properties of engineered tissues are sensitive to hCF doping 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 twitch 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. and . Data are represented as . (e–h) Tissue force amplitude and kinetics were measured as a function of increasing pacing frequency. Active stress (e), upstroke velocity (f), time to 50% relaxation from peak stress (T50 (g)), and time to 90% relaxation from peak stress (T90 (h)) are shown normalized to 5% hCF tissues at 1 Hz (value reported on graphs). 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% hCF tissues at 1 Hz pacing. versus control at same frequency. independent experiments; the number of tissues per measurement is indicated on each bar. C: cardiomyocyte-only control; 5%, 10%, and 15%: addition of 5%, 10%, or 15% human cardiac fibroblasts, respectively, with the number of cardiomyocytes held constant.