Right ventricular failure secondary to chronic overload in congenital heart diseases: Benefits of cell therapy using human embryonic stem cell–derived.

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Right ventricular failure secondary to chronic overload in congenital heart diseases: Benefits of cell therapy using human embryonic stem cell–derived cardiac progenitors Virginie Lambert, MD, PhD, Elodie Gouadon, PhD, André Capderou, MD, PhD, Emmanuel Le Bret, MD, PhD, Mohamed Ly, MD, Sylvie Dinanian, MD, Jean-Francois Renaud, PhD, Michel Pucéat, PhD, Catherine Rücker-Martin, PhD The Journal of Thoracic and Cardiovascular Surgery Volume 149, Issue 3, Pages 708-715.e1 (March 2015) DOI: 10.1016/j.jtcvs.2014.11.033 Copyright © 2015 The American Association for Thoracic Surgery Terms and Conditions

Figure 1 Characteristics of Wnt3a/BMP2 treated cells sorted with an anti-CD15 antibody. Data are expressed as the ratio of gene expression in CD15+ cells versus the CD15−, after normalization with GAPDH for Goosecoid (Gsc), brachyury (T) MesP1, Tbx6, Nkx2.5, and Isl1 (A). Staining of CD15+ cells plated for 12 hours on fibronectin-coated coverslips with an anti-MesP1 antibody (Bioss Inc, Woburn, Mass) and Dapi (DNA, nuclei) (B); bar = 50 μm. DNA, Desoxuribose nucleic acid. The Journal of Thoracic and Cardiovascular Surgery 2015 149, 708-715.e1DOI: (10.1016/j.jtcvs.2014.11.033) Copyright © 2015 The American Association for Thoracic Surgery Terms and Conditions

Figure 2 Hemodynamic parameters issued from pressure-volume loop measurements. A, RV functional parameters: cardiac index and effective ejection fraction; B, contractility index: Emax value; and C, energetics parameters: stroke work and pressure volume area. Values at baseline, 4 months (4 m), 7 months (7 m), for treated (black, n = 6) and sham (white, n = 6) animals, are plotted. *P < .05; PVA, Pressure volume area. The Journal of Thoracic and Cardiovascular Surgery 2015 149, 708-715.e1DOI: (10.1016/j.jtcvs.2014.11.033) Copyright © 2015 The American Association for Thoracic Surgery Terms and Conditions

Figure 3 Total fibrosis (A) and its distribution in interstitial (B) and peri-myocyte (C) localization after cell therapy. Values at 7 months for treated (black, n = 6) and sham (white, n = 6) animals are plotted with lines indicating median. D, Representative longitudinal tissue sections from sham and treated (7 months) animals after Picrosirius red; bar = 100 μm. **P < .01. The Journal of Thoracic and Cardiovascular Surgery 2015 149, 708-715.e1DOI: (10.1016/j.jtcvs.2014.11.033) Copyright © 2015 The American Association for Thoracic Surgery Terms and Conditions

Figure E1 Evolution of the right ventricle area (A) and cardiac myocyte diameters (B) during right ventricle chronic overload. Representative transversal tissue sections from nonoperated and operated sham (4 months), and operated sham (7 months) animals after Picrosirius red; bar = 100 μm (C). *P < .05, **P < .01. The Journal of Thoracic and Cardiovascular Surgery 2015 149, 708-715.e1DOI: (10.1016/j.jtcvs.2014.11.033) Copyright © 2015 The American Association for Thoracic Surgery Terms and Conditions

Figure E2 Evolution of the total fibrosis (A) and its distribution in interstitial (B), and peri-myocyte (C) localization during right ventricle chronic overload and after cell therapy. The 4 months data set shows results of new analyses of samples issued from animals described in our previous study.10 Values at 4 months (4 m) and 7 months (7 m), for nonoperated and operated sham (black) and treated (gray) animals are plotted with lines indicating median. Fibrosis was significantly reduced in treated animals, back to the control level, assessing its complete regression. D, Representative longitudinal tissue sections from nonoperated and operated sham (4 months), and operated sham (7 months) animals after Picrosirius red; bar = 100 μm. Kruskall-Wallis analysis of variance (Dunn's post hoc test); *P < .05, **P < .01. The Journal of Thoracic and Cardiovascular Surgery 2015 149, 708-715.e1DOI: (10.1016/j.jtcvs.2014.11.033) Copyright © 2015 The American Association for Thoracic Surgery Terms and Conditions