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Biomaterial Control of Therapeutic Stem Cells

Biomaterial Control of Therapeutic Stem Cells

Akon Higuchi

(2019)

Abstract

Human pluripotent stem cells (hPSCs), which cover both human embryonic stem cells (hESCs) and induced pluripotent stem cells (iPSCs), show promise for drug discovery and regenerative medicine applications. These stem cells cannot be cultured on conventional tissue culture dishes but on biomaterials that have specific interactions with the hPSCs. Differentiation is regulated by the biological and physical cues conferred by the biomaterial. This book provides a systematic treatment of these topics bridging the gap between fundamental biomaterials research of stem cells and their use in clinical trials.

The author looks at hPSC culture on a range of biomaterial substrates. Differentiation and control of hESCs and iPSCs into cardiomyocytes, osteoblasts, neural lineages and hepatocytes are covered. The author then considers their translation into stem cell therapies and looks at clinical trials across spinal cord injury, macular degeneration, bone disease and myocardial infarction. Finally, a chapter on future directions closes the book. By using this book, the reader will gain a robust overview of current research and a clearer understanding of the status of clinical trials for stem cell therapies.


Table of Contents

Section Title Page Action Price
Cover Cover
Preface v
Abbreviations vii
Contents xiii
Chapter 1 Introduction 1
1.1 Introduction 1
1.2 Stem Cells 1
1.3 The Extracellular Matrix 4
1.4 hPSC Culture on Biomaterials 4
1.5 hPSC Differentiation on Biomaterials 5
1.6 Biomaterials Control hPS Cell Differentiation Fate 6
1.7 Stem Cell Therapy Using Biomaterials 7
References 7
Chapter 2 Adult Stem Cell Culture on Extracellular Matrices and Natural Biopolymers 12
2.1 Introduction 12
2.2 Chemical and Biological Interactions of ECM Proteins and Stem Cells 12
2.3 Collagen 15
2.3.1 Collagen Type I Scaffold 16
2.3.2 Organic Hybrid Scaffold Made of Collagen Type I 23
2.3.3 Scaffolds Using Collagen Type II and Type III 27
2.3.4 Hybrid Collagen Scaffold Using Inorganic Materials 31
2.3.5 Collagen Scaffolds Immobilized Antibody Targeting Stem Cells 33
2.3.6 Differentiation into Endoderm and Ectoderm Lineages Using Collagen Scaffolds 34
2.4 Gelatin 35
2.4.1 Gelatin Hydrogels and Scaffolds 35
2.4.2 Gelatin Hybrid Scaffolds 38
2.5 Laminin 40
2.6 Fibronectin 47
2.7 Vitronectin 49
2.8 Fibrin 51
2.9 Decellularized ECM 52
2.10 Biomaterials with ECM-mimicking Oligopeptides 58
2.10.1 MS Cell Differentiation on Self-assembled ECM-peptide Nanofibers 59
2.10.2 Osteogenic Induction on ECM-peptide Immobilized Dishes and Scaffolds 64
2.10.3 Chondrogenic Induction on ECM-peptide Immobilized Dishes and Scaffolds 65
2.10.4 Neural Induction on ECM-peptide Immobilized Dishes and Scaffolds 68
2.11 Biomaterials with N-Cadherin Mimicking Oligopeptides 69
2.12 Conclusion and Future Perspective 71
References 71
Chapter 3 Feeder-free and Xeno-free Culture of Human Pluripotent Stem Cells on Biomaterials 86
3.1 Introduction 86
3.2 Analysis of the Pluripotency of hPS Cells 86
3.3 2D Cultivation of hPS Cells on Biomaterials 94
3.3.1 hPS Cell Cultivation on ECM-immobilized Surfaces in 2D 94
3.3.1.1 FN (Fibronectin) 95
3.3.1.2 LN (Laminin) 97
3.3.1.3 VN (Vitronectin) 97
3.3.2 hPS Cell Cultivation on Oligopeptide-immobilized Surfaces in 2D 98
3.3.3 hPS Cell Cultivation on a Recombinant E-cadherin Surface in 2D 103
3.3.4 hPS Cell Cultivation on Biomaterials Immobilized with Polysaccharide in 2D 105
3.3.5 hPS Cell Cultivation on Synthetic Biomaterials in 2D 109
3.3.5.1 Synthetic Polymeric Materials That Maintain the Long-term Cultivation of hPS Cells 110
3.3.5.2 Thermoresponsive Polymeric Materials That Maintain the Long-term Cultivation of hPS Cells 112
3.3.5.3 Synthetic Microfibrous Scaffolds That Maintain the Long-term Cultivation of hPS Cells 118
3.4 Three-dimensional Cultivation of hPS Cells on Biomaterials 119
3.4.1 The 3D Cultivation of hPS Cells on Microcarriers 121
3.4.2 The 3D Cultivation of hPS Cells Embedded in Hydrogels (Microcapsules) 126
3.5 hPS Cell Cultivation on PDL-coated Dishes with Small Molecules 130
3.6 Conclusion and Future Perspectives 131
Acknowledgments 133
References 133
Chapter 4 Differentiation Fates of Human ES and iPS Cells Guided by Physical Cues of Biomaterials 141
4.1 Introduction 141
4.2 Induction Protocols of Human Pluripotent Stem Cells 145
4.2.1 EB Formation 147
4.2.2 Induction of hPS Cells by EB Generation 149
4.2.2.1 Type AB Differentiation of hPS Cells 150
4.2.2.2 Type A Differentiation of hPS Cells 151
4.2.2.3 Type B Differentiation of hPS Cells 153
4.2.2.4 Type C Differentiation of hPS Cells 153
4.2.2.5 hPS Cell Induction in Type D 153
4.2.3 Induction of hPS Cells Seeded on Materials Directly 155
4.2.3.1 Type E Differentiation of hPS Cells (2D Cultivation) 155
4.2.3.2 Type E Differentiation of hPS Cells (3D Cultivation) 156
4.2.3.3 Type F Differentiation of hPS Cells 157
4.2.3.4 Type G Cell Differentiation of hPS Cells 158
4.2.3.5 Type H Differentiation of hPS Cells 160
4.3 Physical Cues of Materials in hPS Cell Induction 162
4.3.1 Effect of Elasticity of Cell Cultivation Biomaterials on Stem Cell Induction 162
4.3.1.1 Stiffness of Biomaterials Guides Stem Cell Fate of Differentiation in 2D Cultivation 163
4.3.1.2 Pluripotent Maintenance of MS, iPS, and ES Cells on Soft Biomaterials 171
4.3.1.3 Mechanism of Stem Cell Induction by Substrate Elasticity and ECM in 2D Cultivation 173
4.3.1.4 Biomaterial Stiffness Guides Stem Cell Fate of Differentiation in 3D Cultivation 175
4.3.1.5 Results Contradictory to Engler’s Study in 2D Cultivation 181
4.3.1.6 Contradictory to Engler’s Research in 3D Cultivation 185
4.3.2 Topographic Effects of Biomaterials on the Differentiation Fates of hPS Cells 186
4.3.2.1 Preparation of Nano- and Micropatterned Materials 189
4.3.2.2 Uniform EB Generation in Micropatterned Surface 192
4.3.2.3 Osteogenic and Adipogenic Induction of Stem Cells on Micropatterned Biomaterials 192
4.3.2.4 Hepatic, Myogenic, and Chondrogenic Induction of Stem Cells on Micropatterned Biomaterials 198
4.3.2.5 NS Cell Induction on Micropatterned Biomaterials 202
4.3.3 Stem Cell Induction on Nanofibers 210
4.3.3.1 Stem Cell Differentiation on Nanofiber Made by Self-assembly of Amphiphile Peptides 210
4.3.3.2 Stem Cell Differentiation on Nanofibers Generated by Electrospinning Methods 216
4.3.3.2.1 Size Effect of Nanofibers on Stem Cell Induction 221
4.3.3.2.2 Effect of Nanofiber Alignment on Stem Cell Induction 221
4.3.3.2.3 Stem Cell Induction on Hybrid Nanofiber 228
4.3.3.3 Stem Cell Induction on Nanofibers Prepared Using Phase Separation 229
4.3.4 Effect of Electrical and Mechanical Forces of Biomaterials on Induction Fate of hPS Cells 232
4.4 Conclusions and Perspectives 236
References 237
Chapter 5 Biomaterial Control of Differentiation of Human Embryonic Stem Cells and Induced Pluripotent Stem Cells 252
5.1 Introduction 252
5.2 Induction of hPS Cells into Neural Lineages 258
5.2.1 Stromal-induced Differentiation into Neural Lineages 265
5.2.2 Induction into Neural Lineages Through EB Generation 266
5.2.3 Direct Induction into Neural Lineages on Materials with No EB Generation 266
5.2.4 Effect of Cell Cultivation Materials on hPS Cell Induction into Neural Lineages 269
5.3 Induction of hPS Cells into Cardiomyocytes 276
5.3.1 Efficient Protocols for Inducing hPS Cells into Cardiomyocyte 277
5.3.2 Effect of Cell Cultivation Materials on hPS Cell Induction into Cardiomyocytes 287
5.4 Induction into Hepatocytes 296
5.4.1 Efficient Protocols for hPS Cell Induction into Hepatocytes on Materials 296
5.4.2 3D Cultivation Facilitates the Induction of hPS Cells into Hepatocytes 303
5.4.3 Effect of Cell Culture Biomaterials on hPS Cell Differentiation into Hepatocytes 309
5.5 Differentiation into Insulin-secreting β Cells 311
5.6 Conclusions and Perspectives 316
Acknowledgments 317
References 318
Chapter 6 Clinical Trials of Stem Cell Therapies Using Biomaterials 328
6.1 Introduction 328
6.2 Stem Cell Therapy for Myocardial Infarction (MI) in Clinical Trials 329
6.2.1 Clinical Therapies for MI Using hES cells 330
6.2.1.1 Fibrin Patch Including hES Cell-derived Cardiac Progenitors 330
6.2.1.2 Clinical Trials With Fibrin Patch Including Cardiac Progenitors Derived from HES Cells 332
6.2.1.3 Mechanism of Enhanced Function by Fibrin Patches 333
6.2.2 Clinical Therapy for MI Using Fetal and Adult Stem Cells 333
6.2.2.1 MI Therapy Using Fetal and Adult Stem Cells 333
6.2.2.2 MI Therapy Using Human BMN Cells 337
6.2.2.3 MI Therapy Using CXCR4+ CD34+ Progenitor Cells 338
6.2.2.4 MI Therapy Using Allogeneic and Autologous HMS Cells 339
6.2.2.5 MI Therapy Using Autologous Cardiosphere-derived Cells and Cardiac Stem Cells 340
6.2.2.6 MI Therapy Using Fetal Stem Cells 344
6.2.2.7 MI Therapy Using Adipose-derived Stem (ADS) Cells 345
6.2.3 Future Trends of MI Therapy Using Stem Cells 346
6.3 Stem Cell Therapy for Macular Degeneration Disease in Clinical Trials 346
6.3.1 Macular Degeneration Diseases and Eye Structure 347
6.3.2 Bioengineering in Stem Cell Therapies for Macular Degeneration Diseases 351
6.3.3 Biomaterial Assists in the Therapies for Macular Degeneration Diseases 353
6.3.4 Bioengineering for Clinical Trials Using hES Cell-derived RPE Cells 358
6.3.5 Bioengineering for Clinical Trials Using hiPS Cell-derived RPE Sheets 359
6.3.6 Bioengineering for Clinical Trials Using Adult Stem Cells 361
6.3.7 Clinical Trials Using Fetal Stem Cells 363
6.3.8 Future Perspectives of Stem Cell Therapy for Macular Degeneration Diseases 365
References 366
Chapter 7 Conclusions and Future Perspective on Biomaterial Control of Therapeutic Stem Cells 374
7.1 Introduction 374
7.2 Chapter 1 374
7.3 Chapter 2 374
7.4 Chapter 3 376
7.5 Chapter 4 378
7.6 Chapter 5 379
7.7 Chapter 6 381
References 383
Subject Index 386