Therapeutic Applications of Cell Microencapsulation (eBook)

José Luis Pedraz has a PhD in Pharmacy from the University of Salamanca, Spain. He is professor of Pharmacy and Pharmaceutical Technology at the Faculty of Pharmacy in the Basque Country University. He is cofounder and director of the Pharmaceutical Development Unit of the Basque Country. His interest is focused in the development and evaluation of pharmaceutical dosage forms (microcapsules, micro- and nanoparticles) for the administration of gene, proteins, peptides, vaccines and cells. He has published over 200 scientific articles and edited several book chapters focused on cell microencapsulation. Gorka Orive has a PhD in Pharmacy and is currently assistant professor of Pharmacy and Pharmaceutical Technology at the University of the Basque Country in Vitoria, Spain. He is director of research publications and scientific coordinator of the field of oral implantology for Biotechnology Institute (BTI, Vitoria, Spain). His interests include polymer-based cell therapy for long-term and controlled protein and growth factor delivery to different tissues including brain. He is also interested in the potential use of autologous platelets growth factors and fibrin scaffold for regenerative medicine. He has published more than 100 articles in national and international journals including Nature Medicine, Nature Reviews Neurosciences, Molecular Therapy, Biomaterials, Trends in Pharmacological Sciences among others and several book chapters focused on cell microencapsulation for therapeutic purposes and the use of plasma rich in growth factors in medicine.

Title Page 3
Copyright Page 4
DEDICATION 5
FOREWORD 6
PREFACE 8
ABOUT THE EDITORS... 10
ABOUT THE EDITORS... 11
PARTICIPANTS 12
Table of Contents 15
ACKNOWLEDGEMENTS 19
Chapter 1 Highlights and Trends in Cell Encapsulation 20
Introduction 20
Pivotal Issues for the Progress in the Field 21
Therapeutic Applications of Cell Encapsulation Technology 22
Conclusion 23
References 23
Chapter 2 Biomaterials in Cell Microencapsulation 24
Introduction 24
Alginate 25
Nature and Composition 25
Biocompatibility and Purification of Alginates 25
Properties: Stability, Permeability and Viscosity 28
Alginate Microcapsules: Different Ions and Coatings 29
Cross-Linking Ions 29
Coatings 30
Modifications and Innovations 31
Other Polymers and Type of Biomaterials 33
Conclusion 35
References 35
Chapter 3 Development of Subsieve-Size Capsules and Application to Cell Therapy 41
Introduction 41
Narrow Dispersed Subsieve-Size Capsule Production Via the Jetting Process 42
Effect of Preparation Process on Mammalian Cells 45
Effect of Reduction in Microcapsule Diameter 46
Conclusion 47
References 48
Chapter 4 Regulatory Considerations in Application of Encapsulated Cell Therapies 50
Introduction 50
Background 51
Good Manufacturing Practice 51
FDA 54
Cell-Based Therapies 54
Conclusion 56
References 56
Chapter 5 Treatment of Diabetes with Encapsulated Islets 57
Introduction 57
Concepts of Encapsulation 58
Intravascular Designs 58
Extravascular Macrocapsules 60
Host Responses and Macroencapsulation 61
Extravascular Microcapsules 61
Biocompatibility and Microcapsule Composition 63
Biology of Encapsulated Cells 64
Conclusion 65
References 67
Chapter 6 Epo Delivery by Genetically Engineered C2C12 Myoblasts Immobilized in Microcapsules 73
Introduction 73
Therapeutic Applications Beyond Erythropoiesis 74
Novel Erythropoiesis Stimulating Strategies: Potential New Treatments for Anemia 74
Cell Encapsulation Technology as an Alternative to Frequent Dosing Schemes 76
Conclusion 82
References 82
Chapter 7 Artificial Cell Microencapsulated Stem Cells in Regenerative Medicine, Tissue Engineering and Cell Therapy 87
Introduction 87
Cell Encapsulation 88
Adult Stem Cells and Their Plasticity 88
Tissue Engineering of Bone Marrow Stem Cells 89
Coencapsulation of Bone Marrow Stem Cells with Hepatoyctes to Enhance Hepatocytes Viability and Function 90
Therapeutic Effect of Encapsulated Bone Marrow Stem Cells on the Liver Failure Model 92
Conclusion 93
References 94
Chapter 8 Microencapsulated Choroid Plexus Epithelial Cell Transplants for Repair of the Brain 99
Introduction 99
Basic Structure and Function of the Choroid Plexus 99
The Central Role of the Choroid Plexus in Brain Development 101
The Choroid Plexus in Aging 102
Choroid Plexus and Neurodegeneration: Alzheimer’s Disease (AD) as an Example 103
Harnessing the Choroid Plexus for Transplantation Therapy: Preliminary Studies 103
Immunoisolation within Alginate Microcapsules Enables the Use of Xenogeneic Choroid Plexus Transplants 104
Characterization of Alginate and Encapsulated Choroidal Epithelial Cells 104
Encapsulated Xenogeneic Choroid Plexus Transplants in Animal Models of Stroke 105
Encapsulated Xenogeneic Choroid Plexus Transplants in a Rat Model of Huntington’s Disease 106
In Vitro and In Vivo Determinations of the Effect of Age on CP Function 107
Encapsulated Xenogeneic Choroid Plexus Transplants in a Monkey Model of Huntington’s Disease 108
Conclusion 108
References 109
Chapter 9 Therapeutic Application of Cell Microencapsulation in Cancer 111
Introduction 111
Preclinical Studies of Treatments with Therapeutic Products Produced from Encapsulated Cells 112
Anti-Angiogenic Agents 112
Endostatin 112
Angiostatin 114
Cytokines 115
Antibodies 115
Targeting Chemotherapy 116
Clinical Trials of Cancer Treatment Using Encapsulated Cells to Target Chemotherapy 117
Combination Therapies—The Way for the Future? 119
Retrovirus Vector Production from Encapsulated Cells 119
Conclusion 121
References 121
Chapter 10 Inorganic Nanoporous Membranes for Immunoisolated Cell-Based Drug Delivery 123
Introduction 123
Cell-Based Drug Delivery 124
Immunosuppressed Cell Transplantation 125
Immunoisolated Cell-Based Drug Delivery 125
Origins 125
Intravascular Chambers 126
Motivation 126
Development 126
Commercialization 126
Failure Modes 126
Microcapsules 126
Motivation 126
Development 127
Commercialization 127
Failure Modes 127
Extravascular Chambers 128
Motivation 128
Development 128
Commercialization 129
Failure Modes 130
Inorganic Nanoporous Membranes 130
Silicon Nanoporous Membranes 130
Preparation 130
Advantages 131
Disadvantages 132
Alumina Nanoporous Membranes 133
Preparation 133
Advantages 134
Disadvantages 135
Titania Nanoporous Membranes 136
Preparation 136
Advantages 138
Disadvantages 139
Conclusion 141
References 141
Chapter 11 Cell Microencapsulation 145
Introduction 145
Why Is Microencapsulation Necessary? 145
Immune Protection by a Semipermeable Membrane 145
Molecular Weight Cutoff for Control Permeability 146
Materials for Cell Microencapsulation 147
Geometry of Capsules Matters? 148
Clinical Impact of Microencapsulation Technology 151
Challenges in Cell Microencapsulation 152
Conclusion 153
References 153
Chapter 12 Commercial Applicability of Cell Microancapsulation: A Review of Intellectual Property Rights 156
Introduction 156
Retrieval of the Data Base 157
The Teaching of Bibliographic Data 157
More Detailed Discussion of Relevant Prior Art 161
Conclusion 161
Literature 162
Index 164