Structure-function correlations.

<p><b>A</b>. Representative 2,3,5-triphenyltetrazoliumchloride (TTC) sections covering the LV chamber from the apex to the base from all three groups tested. The blue arrowhead indicates the section level that corresponds to the MR images in Figs <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0144523#pone.0144523.g003" target="_blank">3</a>, <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0144523#pone.0144523.g004" target="_blank">4</a> and <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0144523#pone.0144523.g005" target="_blank">5</a>. <b>B</b>. Correlation between the scar mass (g) evaluated separately by LGE images (JD) and by TTC staining (ET). <b>C</b>. Representative tagged CMR images with infarct zone (IZ) defined by the presence of enhancing myocardium, neighboring myocardium as border zone (BZ), and normal myocardium as remote zone (RZ) for the analysis of regional strain, highlighting the contractility differences among the groups. Blue arrowheads indicate the RV insertion and the location of the first segment of each map. <b>D., E., F</b>. Representative diagrams of the averaged strain included in the analysis (the more negative, the greater the contractility). <b>G</b>. Better contractility was observed in the CDC-treated group compared to the placebo. <b>H</b>. Trend towards better effect of CDC therapy on mid-ventricular wall synchrony assessed by CURE ratio. Error bars indicate SEM. * p<0.05, ** p<0.01</p

Side-by-side evaluation of intramyocardial injections and intracoronary infusions of CDCs data.

<p><b>A</b>. The cell treatment effect of both intramyocardial and intracoronary delivery was superior to placebo with no difference between the 2 treatment groups. <b>B</b>. Similar changes were observed in scar size reduction. <b>C</b>. More cells were detected post intramyocardial injections compared to intracoronary delivery at 24hr of evaluation. Intracoronary data from the present study; intramyocardial data replotted from ref. 32. Error bars indicate SEM.</p

Multi-vessel study design and safety.

<p><b>A</b>. Timeline of the study. <b>B</b>., Allogeneic CDC isolation and manufacturing from 2 male donor hearts resulted in a master cell bank and bags of frozen CDCs. <b>C</b>. Effects of cryopreservation on CD105 and CD45 expression of CDCs. <b>D., E., F</b>. TIMI flow post-infusion in each vessel. <b>G., H</b>. TnI bump (7.4ng/ml) was observed at 24hrs in one animal after the stop-flow protocol. Error bars indicate SEM. Abbreviations: MI, myocardial infarction; CDCs, cardiosphere-derived cells; MRI, magnetic resonance imaging; LAD: left anterior descending artery.</p

Single-vessel Study.

<p><b>A</b>. Illustration of stop-flow protocol and <b>B</b>., the continuous-flow protocol. <b>C, D</b>. Box Plots showing serum [TnI] before infusion and 24hrs post infusion (p = ns; normal <0.05ng/ml). <b>E</b>. Short-axis contrast-enhanced images at baseline and 4 weeks after CDC or vehicle infusion showing <b>F</b>. significant changes of ejection fraction in placebo versus either treated group (p = 0.03 placebo vs CDCs stop-flow and p<0.01 placebo vs CDCs continuous-flow). <b>G</b>. Changes in end-systolic volume between baseline and 4 weeks post-infusion (p = 0.02 placebo vs CDCs stop-flow and p = 0.05 placebo vs CDCs continuous-flow), and <b>H</b>., in end-diastolic volume (p = 0.06 placebo vs CDCs stop-flow and p = 0.2 placebo vs CDCs continuous-flow). Changes in scar mass (<b>I</b>, p = 0.08 placebo vs CDCs stop-flow and p<0.01 placebo vs CDCs continuous-flow), <b>J</b>., infarct wall motion (p = 0.04 placebo vs CDCs stop-flow and p = 0.02 placebo vs CDCs continuous-flow) and <b>K</b>., infarct wall thickness between placebo and treated groups (p = ns). Error bars indicate SEM. * p<0.05, ** p<0.01</p

Vessel density and cardiomyocyte hypertrophy.

<p><b>A</b>. Representative immunostaining sections with sma, isolectin B4 and DAPI, 1 month post treatment. <b>B</b>. Vessel density within the IZ (p = 0.05), <b>C</b>., the BZ and <b>D</b>., the RZ in the CDC-treated compared to placebo (Scale bar = 75μm). <b>E</b>. Representative sections immunostained with α-sa and WGA. <b>F., G</b>. Similar cardiomyocyte diameters in all three groups, both in the BZ and in the RZ. Scale bar = 50μm. Abbreviations: IZ, infarct zone; BZ, border zone; RZ, remote zone; sma, smooth muscle actin (red); isolectin B4 (green); DAPI, blue, 4',6-diamidino-2-phenylindole; asa, α-sarcomeric actinin; WGA, wheat germ agglutinin to define the cell borders. Error bars indicate SEM.</p

MRI results in triple-vessel protocol.

<p><b>A</b>. Representative baseline (upper row) and 1 month post-infusion (lower row) short-axis images in all three groups highlighting the decrease in the scar size and the scar thickness. Yellow arrowheads indicate the infarct zone borders. <b>B</b>. Ejection fraction (EF) decreased significantly in the placebo group compared to both CDC-treated groups (p = 0.1 placebo vs CDCs stop-flow and p = 0.05 placebo vs CDCs continuous-flow). <b>C., D., E</b>. Changes in end-systolic and end-diastolic volumes and in scar mass in the treated groups compared to placebo. <b>F</b>. Infarct wall thickening (p = 0.01 placebo vs CDCs stop-flow and p = 0.05 placebo vs CDCs continuous-flow) and <b>G</b>., infarct wall thickness (p = 0.1 placebo vs CDCs stop-flow and p<0.01 placebo vs CDCs continuous-flow) in the placebo compared to both treated groups. Error bars indicate SEM. * p<0.05, ** p<0.01</p