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. Author manuscript; available in PMC: 2019 Jan 11.
Published in final edited form as: Nat Biotechnol. 2018 Jul 2;36(7):597–605. doi: 10.1038/nbt.4162

Figure 1. Effects of hESC-CM Transplantation on Cardiac Function.

Figure 1

(a) Timeline for the efficacy study in which non-human primates received 180 minute ischemia/reperfusion in the mid LAD vascular bed. Cardiac MRI is incorporated to measure cardiac dimensions and function. Electrophysiology studies are also included in the protocol to study the cause, inducibility, and severity of the ventricular arrhythmias. (b) A representative stain of a short-axis cross section of an infarcted NHP control heart with picrosirius red and fast green, where the infarct collagen is red and healthy myocardium is green. The infarct is transmural, with sparing of subendocardial myocardium. These experiments were repeated 4 times for controls and 5 times for hESC-CM treatment, with similar results. Scale bar, 5 mm. (c) Representative short-axis CINE MRI at end-diastolic and end-systolic phases of the cardiac cycle at 4 weeks after treatment (6 weeks after MI). Blood in the chamber appears bright. There is greater ejection of blood in the hESC-CM heart during systole. These experiments were repeated 4 times for controls and 5 times for hESC-CM treatment, with similar results. Scale bar, 1 cm. (d) Plot of left ventricular ejection fraction (LVEF) for individual subjects (4 control animals, blue; 5 hESC-CM treated animals, red) prior to infarction (Pre-MI), at the post-infarction baseline (one day prior to injection) and at 1 month post treatment. All hESC-CM hearts show significant improvement, while there is minimal improvement in controls. (e) Mean LVEF is comparable between groups prior to infarction and at post-infarction baseline but shows a significant improvement after hESC-CM treatment (*P=0.004, paired t-test, df=4). Data are from 4 biologically independent control animals and 5 hESC-CM treated animals. Bars represent mean ± SEM. Individual data points are shown in 1d. (f) Change in LVEF (ΔLVEF) from baseline to 4 weeks is significantly greater in hESC-CM hearts than in controls Data are from 4 biologically independent control animals and 5 hESC-CM treated animals. Bars represent mean ± SEM. (*P=0.004, 2-tailed t-test, df=7). (g) There is a variable trend (P=0.135, paired t-test, df=7) 4) toward increased systolic thickening of the infarcted wall in hESC-CM treated animals. Data are from 4 biologically independent control animals and 5 hESC-CM treated animals. Bars represent mean ± SEM. (h) Extending survival to 12 weeks demonstrates a modest reduction in LVEF in control hearts and further improvement with hESC-CM treatment. This suggests the benefits seen at 4 weeks are stable with the potential for substantial further improvement.