Myocardial Tissue. Engineering. edited by. Tatsuya Shimizu. Katsuhisa Matsuura. I j [[ Publishing. Pan Stanford

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1 Myocardial Tissue Engineering edited by Tatsuya Shimizu Katsuhisa Matsuura Pan Stanford I j [[ Publishing

2 Contents Preface xi 1. Introduction 1 Yuji Haraguchi, Katsuhisa Matsuura, and Tatsuya Shimizu 2a. Variety of Cell Sources 17 Katsuhisa Matsuura 2a.l Introduction 17 2a.2 Paracrine Effects 18 2a.3 Bone Marrow Mononuclear Cells/Peripheral Blood Mononuclear Cells/Endothelial Progenitor Cells 18 2a.4 Mesenchymal Stem Cells 22 2a.5 Skeletal Myoblasts 23 2a.6 Cardiac Stem/Progenitor Cells 24 2a.7 ES Cells/iPS Cells 26 2a.8 Conclusion 27 2b. Cardiomyocyte Differentiation from Stem Cells 33 Shinako Masuda 2b.1 Introduction 33 2b.2 The TGFp Superfamily in Cardiac Differentiation 36 2b.3 The Wnt Signaling Pathway in Cardiac Differentiation 39 2b.4 FGF Signaling in Cardiac Differentiation 42 2b.5 Other Factors Involved in Cardiac Differentiation 43 2c. The Technologies for Stem Cell Expansion and Differentiation 55 Daisuke Sasaki 2c.l Introduction 55

3 vi Contents 2c.2 Expansion of Undifferentiated Human ESCs/iPSCs 56 2c.3 Induction of Cardiac Differentiation 60 2c.4 Enrichment of Cardiomyocytes Cell Therapy for Myocardial Infarction in Clinical Trials 71 Stefano Pietronave and Dehua Chang 3.1 Introduction Safety and Feasibility of Cell Transplantation Route ofadministration Systemic Intravenous Infusion Intracoronary Cell Infusion Intracardiac Injection Functional Results Proposed Mechanisms Problems and Answers Summary and Conclusions 82 4a. Scaffold-Based Tissue Engineering 89 Soichi Takagi 4a.l Introduction 89 4a.2 Natural Hydrogels 90 4a.2.1 Collagen 90 4a.2.2 Gelatin 91 4a.2.3 Fibrin 91 4a.2.4 Alginate 92 4a.2.5 Hyaluronic Acid 92 4a.3 Synthetic Hydrogels 92 4a.3.1 Polyethylene Glycol] 93 4a.3.2 Poly(Glycolic Acid) 93 4a.3.3 Poly(Lactic Acid) 93 4a.3.4 Polyvinyl Alcohol) 94 4a.3.5 Poly(Lactic-co~Glycolic Acid) 94 4a.4 Decellularized Tissues and Organs 95 4a.4.1 Enzymatic Methods 95 4a.4.2 Chemical Methods 96 4a.4.3 Physical Methods 96 4a.5 Conclusion 97

4 Contents vii 4b. Cell Sheet-Based Tissue Engineering 107 Yuji Haraguchi, Noriko Yasuda, Tatsuya Shimizu, Mctsayuki Yamato, and Teruo Okano 4b.l Introduction 107 4b.2 Cell Attachment/Detachment of a Temperature-Responsive Culture Surface and Resulting Cell Sheets 108 4b.3 The Applications of Cell Sheet-Based Tissue Engineering for Regenerative Medicine 110 4b.3.1 4b.3.2 4b.3.3 4b.3.4 4b.3.5 4b.3.6 4b.3.7 4b.3.8 4b.3.9 Two Epithelial Cell Sheets for Corneal Surface Regeneration 110 Several Adult Stem/Progenitor Cell Sheets for Cardiovascular Disease 111 Periodontal Ligament Cell Sheets for Periodontal Tissue Regeneration 111 Epithelial Cell Sheets for Esophageal Regeneration after ESD 112 Chondrocyte Sheets for Articular Cartilage Repair/Regeneration 112 Fibroblast Sheets as a Lung Air Leak Sealant 113 Pancreatic Islet Cell Sheets for Curing Diabetes Mellitus 114 Hepatic Cell Sheets for Functional Hepatic Tissue 115 Thyroid Cell Sheets for Hypothyroidism 117 4b.4 Conclusion 117 5a Scaffold-Based Myocardial Patches 125 Tadashi Sasagawa 5a.l Introduction 125 5a.2 Scaffold Selection for Engineering Cardiac Patches 126 5a.3 Synthetic Materials 128 5a.3.1 Poly(Glycolic Acid) 128 5a.3.2 Poly(Lactide-co-Glycolide) 128 5a.3.3 Poly(Glycolide-co-Caprolactone) 129 5a.3.4 Poly(Lactide-co-Caprolactone) 129

5 viii Contents 5a.3.5 Polyurethane 130 5a.4 Natural Materials 130 5a.4.1 Alginate 130 5a.4.2 Agarose 131 5a.4.3 Collagen Type I 131 5a.4.4 Gelatin 132 5a.4.5 Fibrin 133 5a.4.6 Decelleularized Tissue Matrices 133 5a.5 Conclusion 135 5b. Cell Sheet-Based Myocardial Patches 141 Yutaka Terajima, Yuji Haraguchi, Tatsuya Shimizu, Masayuki Yamato, and Teruo Okano 5b.1 Introduction 141 5b.2 Temperature-Responsive Culture Surface and Cell Sheets 143 5b.3 Stem Cells and Cell Sheet Therapy 143 5b.3.1 Skeletal Myoblast Sheet Patch 143 5b.3.2 Mesenchymal Stem Cell Sheet Patch 146 5b.3.3 Cardiac Progenitor Cell Sheet Patch 147 5b.3.4 Cardiac Cell Sheet Patch 147 5b.3.5 Fabrication of More Functional Cell Sheet-Based Myocardial Patches 148 5b.3.6 Issues to Be Overcome 149 6a. Scaffold-Based Myocardial Tissue Engineering 157 Yuji Haraguchi and Waki Sekine 6a. 1 Introduction 157 6a.2 Tissue Engineering 158 6a.3 In vitro Reconstruction and in vivo Transplantation of Pulsatile Myocardial Tissue by Using Scaffolds and Cardiac Cells 159 6a.4 Pulsatile Human Cardiac Cell Source 163 6a.5 Conclusion 164 6b. Cell Sheet-Based Myocardial Tissue Engineering 171 Yuji Haraguchi and Tatsuya Shimizu 6b.l Introduction 171 6b.2 In vitro Fabrication of Pulsatile Myocardial Tissue by Layering Cell Sheets 173

6 Contents ix 6b.3 In vivo Transplantation of Layered Cardiac Cell Sheets 174 6b.3.1 6b.3.2 6b.3.3 6b.3.4 Rapid Neovascularization after Cardiac Cell Sheet Transplantation 174 Histological Analyses of Transplanted Cardiac Cell Sheets 175 Physiological and Mechanical Analyses of Myocardial Tissue Grafts after Implantation 175 Comparison between Dissociated Cell Injection and Cell Sheet Transplantation 177 6b.4 Therapeutic Effect of Cardiac Cell Sheet Transplantation on Cardiovascular Disease 177 6b.5 Conclusion 178 6c. Vascularization within Engineered Myocardial Tissue 187 Sachiko Sekiya, Megumi Muraoka, and Tatsuya Shimizu 6c.l Introduction 187 6c.2 Biology of Blood Vessel Formation 188 6c.3 Strategies for Fabricating Vascularized 3D Tissues 189 6c.4 Growth Factor Delivery 191 6c.5 Coculture System Using Blood Vessel-Composing Cells 192 6c.6 Technologies for Fabrication of in vitro Vascular Structures 194 6c.7 In vivo Myocardial Tissue Engineering 196 6c.8 Future Views of Vascularization Technologies 197 6d. Organ-Like Tissue Fabrication 203 Hidekazu Sekine 6d.l Introduction 203 6d.2 Scaffold-Based Cardiac Pumps 204 6d.3 Cell Sheet-Based Cardiac Pumps 206 6d.4 Future Perspective 207 6e. Bioreactor Technologies for Myocardial Tissue Engineering 211 Katsuhisa Sakaguchi 6e.l Introduction 211

7 x I Contents 6e.2 Bioreactors under Microgravity 212 6e.3 Hollow-Fiber Bioreactor 213 6e.4 Perfusion Bioreactor 214 6e.5 In vivo Perfusion Bioreactor and in vivo Tissue Culture 215 6e.6 Summary Future Developments 221 Yuji Haraguchi and Tatsuya Shimizu Index 233

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