Extended Data Fig. 5: Real-time metabolic measurement of vascularized cardiac organoids under epinephrine stimulation.
From: Electro-metabolic coupling in multi-chambered vascularized human cardiac organoids
Nested analysis of the organoid’s contraction and oxygen oscillation (a) frequency and (b) amplitude during prolonged stimulation by 100 µM epinephrine in UN-1, ACS-1021, and ACS-1028 cardiac organoids. Analysis shows that epinephrine exposure significantly increases the frequency of cardiac contraction and oxygen oscillations (n = 3, p < 0.001), and the amplitude of cardiac contraction and oxygen oscillation amplitudes (n = 3, p < 0.001). c, Analysis of the kinetic behaviour of the organoid’s contraction rate during prolonged stimulation by 100 µM epinephrine. Kinetic analysis suggests that epinephrine stimulation results in a sigmoidal-like change in the organoid contraction rate. Representative relation graphs between (d) contraction amplitude (contractility) to contraction rate, and (e) interstitial oxygen content to contraction rate during prolonged epinephrine stimulation. Analysis suggests a correlation between an increase in cardiac organoid contractility and oxygen consumption. f, Representative frequency histograms of interstitial oxygen measurements at 0, 15, and 90 minutes after stimulation with 100 µM epinephrine. Analysis shows that an increase in oxygen consumption correlates to an increase in interstitial oxygen content variability correlative to the increased oxygen amplitudes measured. Representative correlation analysis between (g) oxygen oscillation frequency to contraction frequency and (h) oxygen oscillation amplitude to contractility reveals a direct linear correlation between the oscillatory behaviour of the interstitial oxygen and organoid contraction. i, Representative graphs of the cardiac organoid’s contraction and interstitial oxygen content 60 mins prior to epinephrine stimulation and 5 hours post-stimulation with 100 µM epinephrine. Oxygen returns to the baseline value after 300 minutes, indicating hypoxia, stimulation-induced or ischemia-like injuries did not occur. Middle represents mean of 3 biological repeats for each line; error bars,s.e.m. Significance was determined using a two-tailed nested t-test.
