Opportunities in Stem Cell Research and Commercialization: Technology advances, regulatory impact and key players

Table of Contents
Opportunities in Stem Cell Research and
Commercialization
Executive Summary 10
Introduction to stem cells 10
Regulatory and ethical issues 11
Technologies and strategies 12
Market analysis 13
Adult stem cell programs 14
Embryonic and fetal stem cell programs 15
Patents in stem cell research 16
Trends and opportunities 17

Chapter 1 Introduction to stem cells 20
Summary 20
Introduction 21
Stem cell types 21
Differentiated cell types 23
Major milestones in stem cell research 24
Characteristics of embryonic and adult stem cells 26
Current uses of stem cells 29
Potential uses of stem cells 30

Chapter 2 Regulatory and ethical issues 34
Summary 34
Introduction 35
Regulation of cell and tissue therapies (USA) 35
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Ethical issues in embryonic stem cell research 38
Global embryonic stem cell policies 40
USA 41
Europe 43
Israel, Russian Federation and Asian nations 44
Canada and Australia 45

Chapter 3 Technologies and strategies 48
Summary 48
Introduction 49
Culture of adult stem cells 49
Isolation and identification of stem cells 49
Ex vivo expansion 51
Prevention of differentiation in culture 51
Preservation and scale-up 52
Examples of adult stem cell cultures 52
Hematopoietic stem cells 52
Mesenchymal stem cells 55
Neural stem cells 56
Culture of mouse ESCs 57
Culture of human ESCs 59
Single cell cloning 62
Challenges 62
Tissue engineering 64

Chapter 4 Market analysis 68
Summary 68
Introduction 69
The regulation of cellular therapy 69
Human embryonic stem cells (hESCs) 69
Human mesenchymal stem cells (MSCs) 70
Human hematopoietic stem cells (HSCs) 70
Stem cell mobilization 72
Stem cell expansion 73
Stem cell therapy and tissue engineering products 74
Commercial applications 74
Bone/cartilage regeneration 74
Myocardial and vascular regeneration 75
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Pancreatic beta-cell regeneration 75
Neuronal regeneration 76
Skin replacement and wound healing 76
Drug screening 76
Embryonic and fetal stem cell programs 77
Potential markets 77
Overview of stem cell market forecasts 80
The stem cell market, 2005-2010 81
Preliminary observations 81
Quantitative forecasts 82
Stem cell competitive landscape 85
Therapeutic stem cells and research/services 85
Cord blood banks 88
Cytokines 89

Chapter 5 Adult stem cell programs 92
Summary 92
Introduction 93
Hematopoietic stem cell (HSC) transplantation 93
Established clinical applications 94
HSC mobilization products 96
Emerging clinical applications 97
Purification of HSCs for transplantation 98
Harvesting of HSCs from cord blood 98
HSC-based gene therapy 101
Ex vivo expansion systems 102
Mesenchymal stem cells for GvHD 104
In vivo stem cell activation 104
Stem cells for tissue repair/regeneration 106
Tissue repair products 109
Bone/cartilage regeneration 109
Myocardial and vascular regeneration 111
Beta-cell regeneration 116
Neuronal regeneration 118
Skin replacement and wound healing 120
Other applications 121
Novel approaches 122
Stem cells for drug testing applications 124
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Chapter 6 Embryonic and fetal stem cell programs 128
Summary 128
Introduction 129
Human embryonic stem cell (hESC) lines 129
hESC lines derived from blastocyst embryos 129
Other approaches to derivation of hESC lines 131
Somatic cell nuclear transfer 131
Fusion technologies 132
Single-cell embryo biopsy 133
Other approaches 134
Harnessing the power of ESCs 135
Tissue repair/regeneration 135
Initial challenges 136
Directed differentiation of ESCs 137
Nascent therapies 139
Drug screening and discovery 141
Miscellaneous applications 143
Human fetal stem cell therapies 144

Chapter 7 Patents in stem cell research 148
Summary 148
Introduction 149
Patent systems in Europe and the US 150
Overview 150
Post-issue challenges to patent validity 152
Patent litigation 153
Patenting of stem cells 154
Survey of US stem cell patents 156
Methodology 156
Patent activity analysis 157
Competitive analysis 159
Most frequently cited patents 159
Most prolific patent assignees 163

Chapter 8 Trends and opportunities 166
Summary 166
Slow beginnings, big promise 167
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Ensuring a strong proprietary position 168
Exploiting accessible sources of adult stem cells 170
Regenerative medicine takes shape 171
Commercializing stem cells for drug screening 173
Embracing embryonic stem cell research 174

Chapter 9 Appendix 178
Specialist stem cell companies 178
Companies with adult stem cell programs 180
Companies with fetal and embryonic stem cell programs 184
Cord blood banks around the world 187
The top 30 stem cell patent citations 191
Abbreviations 204
Technical Terms 204
Regulatory Terms 205
Index 207
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List of Figures
Figure 1.1: History of stem cell research 25
Figure 4.2: Commercial focus of 106 stem cell companies by type of stem cell program 86
Figure 4.3: Geographic location of 106 specialized stem cell companies 87
Figure 4.4: Ownership status of 106 specialized stem cell companies 88
Figure 4.5: Cord blood banks by region 89
Figure 7.6: US stem cell patents, filed 1980-2005 157
Figure 7.7: Patent activity analysis for types of Stem cells, filed 1980-2005 158
Figure 7.8: Top 30 US stem cell patents: types of stem cell and technology areas 161
Figure 7.9: Top 30 US stem cell patents: therapy area 162
Figure 7.10: Top 30 US stem cell patents by FCN, filed 1980-2005 162

List of Tables
Table 4.1: Potential US patient populations for cell-based therapies, 2005 78
Table 4.2: Annual direct expenditures in the US for selected diseases, 2005 78
Table 4.3: Stem cell market forecasts by technology and product type, 2005-2010 84
Table 4.4: Stem cell market forecasts by region, 2005-2010 85
Table 7.5: Top 30 stem cell patents by forward citations (US filings), 1980-2005 160
Table 7.6: Top 30 assignees for US stem cell patents (US filings 1980-2005) 164
Table 8.7: Specialist companies with proprietary adult stem cells or proprietary technogies 171
Table 8.8: Specialist companies developing autologous and allogeneic therapies for tissue
regeneration/repair 172
Table 9.9: 106 specialist stem cell companies 178
Table 9.10: 106 specialist stem cell companies (cont.) 179
Table 9.11: Commercial exploitation of adult stem cells for blood cancers and other blood diseases
180
Table 9.12: Commercial exploitation of adult stem cells for tissue repair/regeneration 181
Table 9.13: Commercial exploitation of adult stem cells for tissue repair/regeneration (cont.) 182
Table 9.14: Commercial exploitation of adult stem cells: miscellaneous research/services 183
Table 9.15: Programs utilizing human fetal stem cells 184
Table 9.16: Programs utilizing human embryonic stem cells 185
Table 9.17: Programs utilizing animal embryonic stem cells 186
Table 9.18: Cord Blood Banks in the US and Canada 187
Table 9.19: Cord Blood Banks in Mexico, Central and South America 188
Table 9.20: Cord Blood Banks in the UK and rest of Europe 189
Table 9.21: Cord Blood Banks in the Middle East, Asia, Africa, Australia and New Zealand 190