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Injectable Small Intestine Submucosal Extracellular Matrix in an Acute Myocardial Infarction Model  Hadi Daood Toeg, MD, MS, Rashmi Tiwari-Pandey, PhD,

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Presentation on theme: "Injectable Small Intestine Submucosal Extracellular Matrix in an Acute Myocardial Infarction Model  Hadi Daood Toeg, MD, MS, Rashmi Tiwari-Pandey, PhD,"— Presentation transcript:

1 Injectable Small Intestine Submucosal Extracellular Matrix in an Acute Myocardial Infarction Model 
Hadi Daood Toeg, MD, MS, Rashmi Tiwari-Pandey, PhD, Richard Seymour, BS, Ali Ahmadi, MD, Suzanne Crowe, BS, Branka Vulesevic, MS, Erik J. Suuronen, PhD, Marc Ruel, MD, MPH  The Annals of Thoracic Surgery  Volume 96, Issue 5, Pages (November 2013) DOI: /j.athoracsur Copyright © 2013 The Society of Thoracic Surgeons Terms and Conditions

2 Fig 1 Left ventricular ejection fraction (LVEF) improved in both small intestine submucosal extracellular matrix (SIS-ECM)–treated groups. Improved LVEF in SIS-ECM and SIS-ECM + circulating angiogenic cell (CAC) groups is seen compared with phosphate buffered saline (PBS) controls (p = 0.08 and p = 0.06, respectively). The Annals of Thoracic Surgery  , DOI: ( /j.athoracsur ) Copyright © 2013 The Society of Thoracic Surgeons Terms and Conditions

3 Fig 2 Reduction of infarct area in small intestine submucosal extracellular matrix (SIS-ECM)–treated hearts. As compared to (A) phosphate buffered saline (PBS) and (B) circulating angiogenic cell (CAC)-treated groups, Masson’s trichrome–stained sections displayed reduced infarct size in (C) SIS-ECM–treated groups and (D) SIS-ECM + CAC-treated groups. (E) Bar graph demonstrating the reduced infarct size in both SIS-ECM treated groups (**p < 0.002). The Annals of Thoracic Surgery  , DOI: ( /j.athoracsur ) Copyright © 2013 The Society of Thoracic Surgeons Terms and Conditions

4 Fig 3 Augmented angiogenesis in small intestine submucosal extracellular matrix (SIS-ECM)–treated groups. (A) Representative images of α-SMA–positive arterioles (arrow in insert) in hearts after treatment with PBS, (B) circulating angiogenic cells (CACs) only (arrow in insert), (C) SIS-ECM only (arrows in insert), or (D) SIS-ECM + CACs (arrows in insert). (E) Number of arterioles per high-power field (HPF) (**p < compared with phosphate buffered saline [PBS]). (FOV = field of view.) The Annals of Thoracic Surgery  , DOI: ( /j.athoracsur ) Copyright © 2013 The Society of Thoracic Surgeons Terms and Conditions

5 Fig 4 Increased β-catenin localization in intercalated disks in both small intestine submucosal extracellular matrix (SIS-ECM)–treated groups. (A) Disorganized and fragmented β-catenin bordering cardiomyocytes were localized in phosphate buffered saline (PBS) (asterisk in insert) and (B) circulating angiogenic cell (CAC)-only treatment groups (asterisk in insert). Organized β-catenin intercellular adherens junctions were found in (C) SIS-ECM–only and (D) SIS-ECM + CAC-treated groups (arrows in insert). (E) The number of β-catenin–positive junctions per high-power field (HPF) was increased in the CAC-alone group (*p = 0.01), SIS-ECM–alone group (**p < 0.005), and SIS-ECM + CAC group (**p < 0.005) compared with phosphate buffered saline (PBS). The Annals of Thoracic Surgery  , DOI: ( /j.athoracsur ) Copyright © 2013 The Society of Thoracic Surgeons Terms and Conditions

6 Fig 5 Augmentation in the number of GATA4–positive cells per high-power field (HPF) in small intestine submucosal extracellular matrix (SIS-ECM)–treated samples. (A) GATA4 expression in phosphate buffered saline (PBS), (B) in circulating angiogenic cell (CAC)-only treatment groups, (C) in SIS-ECM–only treatment groups, and (D) in SIS-ECM + CAC treatment groups by using immunohistochemical analysis showing newly formed cardiomyocytes (arrows in figure inserts). (E) More GATA4-positive cells were seen per HPF in CACs alone (p = 0.1), SIS-ECM alone (*p = 0.04), and SIS-ECM + CACs (**p = 0.003) compared with PBS controls. The Annals of Thoracic Surgery  , DOI: ( /j.athoracsur ) Copyright © 2013 The Society of Thoracic Surgeons Terms and Conditions

7 Fig 6 Small intestine submucosal extracellular matrix (SIS-ECM) + circulating angiogenic cells (CACs) provided a potential medium for cell engraftment. (A) Fluorescence in situ hybridization (FISH) staining for Y-positive (dark pink signal) chromosomes in wild-type male positive control mice, (B) female mice treated with SIS-ECM–only negative control, (C) experimental CAC-only–treated mice, and (D) SIS-ECM + CAC–treated myocardial sections. Arrows indicate Y chromosome–positive cells (4',6-diamidino-2-phenylindole [DAPI] counterstained). Bar indicates scale of 20 μm. The Annals of Thoracic Surgery  , DOI: ( /j.athoracsur ) Copyright © 2013 The Society of Thoracic Surgeons Terms and Conditions


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