Figure 4.

Recovered hiPSC-CMs Show Altered Drug Response at the Cellular Level

Representative single-cell AP recordings using ASAP2 in line 1 fresh hiPSC-CMs treated with (A) nifedipine, (D) ibutilide, (G) sunitinib, and (J) E4031 with two different doses. Line 1 recovered hiPSC-CMs showed blunted changes in APD50 and APD90 compared with fresh hiPSC-CMs when cells treated with (B and C) nifedipine (fresh, n = 33 [0.01 μM], n = 19 [0.1 μM]; recovered, n = 18 [0.01 μM], n = 21 [0.1 μM]), (E and F) ibutilide (fresh, n = 14 [0.02 μM], n = 15 [0.2 μM]; recovered, n = 23 [0.02 μM], n = 30 [0.2 μM]), (H and I) sunitinib (fresh, n = 13 [0.3 μM], n = 15 [3 μM]; recovered, n = 18 [0.3 μM], n = 15 [3 μM]), and (K and L) E4031 (fresh, n = 22 [0.01 μM], n = 13 [0.1 μM]; recovered, n = 12 [0.01 μM], n = 11 [0.1 μM]). Raw APD50 and APD90 data are presented in (B), (E), (H), and (K). Data of relative change to vehicle are presented in (C), (F), (I), and (L). The cell number of vehicle was 93 and 89 in fresh and recovered groups, respectively, and the same dataset was used for plotting graphs in four drug treatments. Data were collected from three independent dish preparations from two independent differentiations. All data represented as mean ± SEM, ^∗p < 0.05, ^∗∗p < 0.01, ^∗∗∗p < 0.001, and ^∗∗∗∗p < 0.0001 compared with their respective fresh samples at the same dose.