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Sirtuin1 Regulates the Stem Cell Therapeutic Effects on Regenerative Capability for Treating Severe Heart Failure in a Juvenile Animal Model  Hideto Ozawa,

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Presentation on theme: "Sirtuin1 Regulates the Stem Cell Therapeutic Effects on Regenerative Capability for Treating Severe Heart Failure in a Juvenile Animal Model  Hideto Ozawa,"— Presentation transcript:

1 Sirtuin1 Regulates the Stem Cell Therapeutic Effects on Regenerative Capability for Treating Severe Heart Failure in a Juvenile Animal Model  Hideto Ozawa, MD, Shigeru Miyagawa, MD, PhD, Satsuki Fukushima, MD, PhD, Emiko Itoh, PhD, Akima Harada, BD, Atsuhiro Saito, PhD, Takayoshi Ueno, MD, PhD, Koichi Toda, MD, PhD, Toru Kuratani, MD, PhD, Yoshiki Sawa, MD, PhD  The Annals of Thoracic Surgery  Volume 102, Issue 3, Pages (September 2016) DOI: /j.athoracsur Copyright © 2016 The Society of Thoracic Surgeons Terms and Conditions

2 Fig 1 Cytokine pathway of sirtuin1 (SIRT1). (HGF = hepatocyte growth factor; HIF-1 = hypoxia-induced factor-1; NF-κB = nuclear factor-κB; SDF-1 = stromal cell–derived factor-1; TGF-β = transforming growth factor-β; VEGF = vascular endothelial growth factor.) The Annals of Thoracic Surgery  , DOI: ( /j.athoracsur ) Copyright © 2016 The Society of Thoracic Surgeons Terms and Conditions

3 Fig 2 Preparation of the sirtuin1 (SIRT1) gene downregulated skeletal stem cells derived from Lewis rat. (A) The short interfering RNA (SiRNA) of SIRT1, (B) mRNA expression (reverse transcriptase polymerase chain reaction), and (C) SIRT1 protein expression (Western blotting). The Annals of Thoracic Surgery  , DOI: ( /j.athoracsur ) Copyright © 2016 The Society of Thoracic Surgeons Terms and Conditions

4 Fig 3 Serial changes of (A) left ventricular ejection fraction (EF), (B) percentage of strain, and (C) strain rate. (D) Ejection fraction 8 months after the cell sheet transplantation from cardiac magnetic resonance imaging. The Annals of Thoracic Surgery  , DOI: ( /j.athoracsur ) Copyright © 2016 The Society of Thoracic Surgeons Terms and Conditions

5 Fig 4 Histologic examination of (A) percentage of fibrosis, (B) myocardial cell size, and (C) vascular density. The Annals of Thoracic Surgery  , DOI: ( /j.athoracsur ) Copyright © 2016 The Society of Thoracic Surgeons Terms and Conditions

6 Fig 5 Proliferation capacity, (A) the ratio of Ki67-positive cells, (B) doubling time, and (C) the content of vascular endothelial growth factor (VEGF) in the culture supernatant of the skeletal stem cells derived from mini-pigs. (ELISA = enzyme-linked immunosorbent assay.) The Annals of Thoracic Surgery  , DOI: ( /j.athoracsur ) Copyright © 2016 The Society of Thoracic Surgeons Terms and Conditions

7 Fig 6 Angiogenic cytokine gene expressions of the skeletal stem cells derived from mini-pigs. (HGF = hepatocyte growth factor; HIF-1 = hypoxia-induced factor-1; SDF-1 = stromal cell–derived factor-1; VEGF = vascular endothelial growth factor.) The Annals of Thoracic Surgery  , DOI: ( /j.athoracsur ) Copyright © 2016 The Society of Thoracic Surgeons Terms and Conditions

8 Fig 7 (A) sirtuin1 (SIRT1) gene (reverse transcriptase polymerase chain reaction [PCR]) and (B) protein (enzyme immunoassay) expression of the skeletal stem cell. The Annals of Thoracic Surgery  , DOI: ( /j.athoracsur ) Copyright © 2016 The Society of Thoracic Surgeons Terms and Conditions

9 Fig 8 Proliferation capacities, (A) doubling time, and (B) tunnel staining of the sirtuin1 (SIRT1) knockdown (KD) skeletal stem cells. The Annals of Thoracic Surgery  , DOI: ( /j.athoracsur ) Copyright © 2016 The Society of Thoracic Surgeons Terms and Conditions

10 Fig 9 Angiogenic cytokine secretion capacities of the sirtuin1 (SIRT1) knockdown (KD) skeletal stem cells. (HGF = hepatocyte growth factor; SDF-1 = stromal cell–derived factor-1; VEGF = vascular endothelial growth factor.) The Annals of Thoracic Surgery  , DOI: ( /j.athoracsur ) Copyright © 2016 The Society of Thoracic Surgeons Terms and Conditions

11 Fig 10 (A) The survival potential, (B) serial changes of ejection fraction, and (C) histologic examination (10C) after the sirtuin1 (SIRT1) knockdown (KD) skeletal stem cell sheet transplantation for Lewis rats. The Annals of Thoracic Surgery  , DOI: ( /j.athoracsur ) Copyright © 2016 The Society of Thoracic Surgeons Terms and Conditions


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