Translational Stem Cell Research (eBook)

Issues Beyond the Debate on the Moral Status of the Human Embryo

Kristina Hug, Göran Hermerén (Herausgeber)

eBook Download: PDF

2010 | 2011
XXVI, 462 Seiten
Humana Press (Verlag)
978-1-60761-959-8 (ISBN)

Infos

For many years, the ethical discussion surrounding human embryonic stem cell research has focused on the moral status of the embryo. This text takes a wider moral berth and focuses on numerous ethical, legal and social aspects involved in translating the results of stem cell research into diagnostic and therapeutic applications. Translational Stem Cell Research is broken into ten sections. It opens with an overview of the latest in stem cell research, focusing on specific diseases and the treatment of burn victims. Part II discusses the issues involved in the many steps from bench to bedside, ranging from first research in vitro to clinical trials. Part III covers scientific, regulatory and ethical challenges to basic research, and Part IV details issues regarding stem cell banks. Part V explores ethical, economic and strategic issues involved in collaboration between universities and industry, and Part VI addresses legal problems raised by patents on human stem-cell based inventions plus the extent to which there can be technological solutions to a moral dilemma. Part VII presents imaginative ways of communicating research to the general public and how to create conditions for a constructive dialogue. Part VIII probes psychosocial and cultural factors affecting judgment and decisions about translational stem cell research, and Part IX explores problems and procedures raised by an examination of the evaluation of stem cell research projects in research ethics committees. The book closes with a look into the future of translational stem cell research and stem cell-based therapeutic applications.

Inhalt

Translational Stem Cell Research 3
Preface 5
Contents 9
Biosketches 13
Editors 13
Contributors 14
Part I Translational Stem Cell Research:What is PossibleToday and What Still Remains to be Achieved? 27
Chapter 1: Towards Clinical Application of Stem Cells in Neurodegenerative Disorders 28
1.1 Introduction 28
1.2 Moving Stem Cells to the Clinic in Neurodegenerative Disorders: General Aspects 29
1.3 Stem Cell Therapy for PD 30
1.4 Stem Cell Therapy for AD 33
1.5 Stem Cell-Based Therapies for Stroke 34
1.6 Perspectives 37
References 38
Chapter 2: Treating Cardiac Disorders with Stem Cells 40
2.1 Introduction 40
2.2 Adult Stem Cells 41
2.3 Pluripotent (Embryonic) Stem Cells and Cardiac Progenitors: Sources of Cardiomyocytes 43
2.4 Summary and Conclusions 45
References 46
Chapter 3: Treating Diabetes 48
3.1 Introduction 49
3.2 Insulin, the Beta Cell and Two Major Types of Diabetes 49
3.3 Cell Therapy of Diabetes to Normalize Blood Sugar Levels 50
3.4 Therapeutic Beta Cells from Stem cells? 50
3.5 Tackling Immunological Compatibility and Autoimmunity 52
3.5.1 Adult Stem Cell-Mediated Correction of Autoimmunity? 53
3.5.2 Pluripotent Stem Cell-Mediated Tolerization Towards Therapeutic Cells 53
3.5.3 iPS Derived Beta Cells from Patients to Devise New Strategies to Understand and Prevent Autoimmune Diabetes 54
3.6 Future Outlook 54
3.6.1 Improved In Vitro Differentiation Protocols for ES Cells and iPS Cells 54
3.6.2 Improved Transplantation, Including Encapsulation or Immunomodulation (Non-myeloablative Induced Tolerance by Mixed Chimerism) 55
References 55
Chapter 4: Treating Oncologic Disease 60
4.1 Introduction 61
4.2 Developmental Cancers 62
4.2.1 Teratocarcinomas and Germ Cell Tumors 62
4.2.2 Leukemia 64
4.2.3 Other Developmental Tumors 65
4.3 Prospective 66
References 67
Chapter 5: Clinical Application of Autologous Epithelial Stem Cells in Disorders of Squamous Epithelia 69
5.1 Introduction 69
5.2 The Epidermis and the Cornea 70
5.3 Future Challenges 72
5.3.1 Comprehending Engraftment 72
5.3.2 Stem Cell Plasticity 73
5.3.3 Ex Vivo Gene Therapy 73
5.3.4 Embryonic Stem Cells and iPS 74
References 74
Chapter 6: Towards a Cell Therapy for Muscular Dystrophy: Technical and Ethical Issues 78
6.1 Introduction 78
6.2 The Muscular Dystrophies 79
6.3 Strategies to Replace Affected Cells 79
6.4 Bone Marrow-derived Stem Cells 80
6.5 Mesoangioblasts 80
6.6 Future Autologous Cell Transplantation 81
6.7 Patient Selection 82
6.8 Donor Selection 83
6.9 Costs 83
6.10 Conclusions 84
References 84
Chapter 7: Towards Modeling and Therapy of Genetic Diseases Using Pluripotent Stem Cells 87
7.1 Introduction 88
7.2 Advantages and Limitations of Genetic Disease Modeling Using Pluripotent Stem Cells 89
7.3 Strategies for Establishing Models of Human Genetic Diseases from Pluripotent Stem Cells 90
7.4 Recent Advances in Modeling and Therapy of Human Genetic Diseases Using Embryonic and Induced Pluripotent Stem Cells 92
7.5 Future Challenges and Directions 94
References 95
Chapter 8: Therapeutic Possibilities of Induced Pluripotent Stem Cells 99
8.1 Pluripotent Stem Cells: Potential and Pitfalls 99
8.2 Therapeutic Promise 101
8.2.1 iPS Cells and Cell Therapy 102
8.2.2 iPS Cells and Disease Modeling 104
8.2.3 Pharmaceutical Applications of iPS Cells 106
8.2.4 Stem Cell Surveillance in Vivo 107
8.3 Conclusion and Future Directions 107
References 108
Chapter 9: Industrial Applications of Stem Cells 113
9.1 Introduction 114
9.2 Pluripotent Stem Cells – Their Sourcesand Characterization 114
9.3 Induced Pluripotent Stem Cells (iPS) 115
9.4 Prospects and Challenges Associated with the Clinical Application of Induced Pluripotent Stem Cells 118
9.5 Prospects of iPS Cells for Cell-based Disease Modelling and Compound Development 119
9.5.1 IPS Cell Applications in Other Species 120
9.6 The Potential of Pluripotent Stem Cells for Industrial Use in Compound Screening 120
9.7 Challenges on the Way to Industrial Applications of Stem Cells 121
9.8 Concluding Remarks 122
References 123
Chapter 10: The Obstacles on the Road to ClinicalApplications of Stem Cell-Based Therapies: What Has Been Done to Overcome These Obstacles and What Remains to Be Done? 125
10.1 Introduction 126
10.2 The Expected First Clinical Applications 126
10.3 Risks in Stem Cell Transplantation 127
10.3.1 Infections and How to Avoid Them 127
10.3.2 Immunogenicity 128
10.3.3 Tumorigenicity 129
10.3.3.1 Pluripotency-Related Tumors 129
10.3.3.2 Culture Adaptation 129
10.3.3.3 How to Detect Possible Tumor-Forming Cells, and How to Remove Them 130
10.4 Prospective 131
References 131
Part II Translating Stem Cell Research Knowledgefrom Bench to Bedside: Ethical Issues 133
Chapter 11: Translational Stem Cell Research and Animal Use: Examining Ethical Issues and Opportunities 134
11.1 Introduction 134
11.2 Animal Use in Research 136
11.3 Animal Use, 3Rs and Stem Cell Research 138
Refinement and Reduction 139
Replacement 140
11.4 Applying Ethical Frameworks to Assist Decision-Making 141
11.5 Future Challenges 143
References 144
Chapter 12: Ethical Aspects of Stem Cell-Based Clinical Translation: Research, Innovation,and Delivering Unproven Interventions 146
12.1 Introduction 146
12.2 Translational Research 147
Ethical Frameworks 150
12.3 Medical Innovation 150
Ethical Frameworks 151
12.4 Clinical Use of Unproven Interventions 153
Ethical Frameworks 154
12.5 Concluding Comments 155
References 155
Chapter 13: Translational Stem Cell Research in Pediatrics: Ethical Issues 157
13.1 Introduction 158
13.2 The Requirement of Informed Consent in Research on Humans 158
13.3 Pediatrics and Its Demand for Scrutinized Procedures and Products 159
13.4 Research Without Informed Consent 159
13.5 Features of Stem Cell Therapy 162
13.6 Strategies of Ethically Justifying Translational Stem Cell Research on Minors 165
13.7 Conclusion 167
References 167
Chapter 14: Experimental Stem Cell-Based Therapyin Pediatrics: A Fictional Case Study 170
14.1 Introduction 171
14.2 Experimental Stem Cell-Based Therapies in Pediatrics – Are They Justified? 173
14.2.1 Must Children Be Involved to Answer the Research Question? 174
14.2.2 The Difficult Balance Between Risk of Harm and Expected Benefit 175
14.2.2.1 Consequentialist Arguments 177
14.2.2.2 Arguments Based on Human Rights 178
14.2.2.3 Dignitarian Arguments 179
14.2.2.4 Other Deontological Arguments 180
14.2.3 Free and Informed Consent in the Contextof Experimental Stem Cell-Based Therapies 181
14.3 Epilogue 183
References 183
Part III Creation of Human-Animal Entities for TranslationalStem Cell Research: Scientific, Ethicaland Regulatory Challenges 186
Chapter 15: Creation of Human–Animal Entitiesfor Translational Stem Cell Research: ScientificExplanation of Issues That Are Often Confused 187
15.1 Introduction 187
15.2 Classifying Interspecies Entities 188
15.2.1 Interspecies Hybrids 191
15.2.2 Cybrids and Transgenic Animals 191
15.2.3 Different Categories of Chimeras 193
15.3 Developmental Human–Nonhuman Chimerasand Associated Issues 196
15.4 Distinguishing Humans from Other Animals 198
15.5 Interspecies Entities and Human Identity 200
References 204
Chapter 16: Chimeras and Hybrids – How to Approach Multifaceted Research? 210
16.1 Introduction 210
16.2 Definitions 211
16.3 Structuring the Ethical Debate 212
16.3.1 Intra- Versus Interspecific Hybrids and Mosaics 212
16.3.2 Sources, Donors, and Introduced Material 213
16.3.3 Recipient Species 214
16.3.4 Developmental Stage of the Recipient and Transplantation Side 214
16.3.5 Research Aims, Possible Uses, Side Effects 215
16.4 Example 215
16.4.1 Intra- Versus Interspecific Hybrids and Mosaics, as well as Recipient Species and Experimental Setting 216
16.4.2 Developmental Stage of the Recipient, Transplantation Side 216
16.4.3 Sources, Donors, and Introduced Material 217
16.4.4 Research Aims Possible Uses Chances, Risks and Side Effects Alternatives217
16.4.4.1 Transplantation Medicine 218
16.4.4.2 Tentative Appraisement of the Case 219
16.5 Fundamental Ethical Problems and Open Questions 219
16.5.1 Animals and Species 219
16.5.2 The Use of Human Embryos/Fetuses 222
16.6 Conclusion 224
References 224
Chapter 17: Chimeras + Hybrids = Chimbrids: Legal Aspects 227
17.1 Introduction 227
17.2 Legal Aspects 229
17.2.1 The Regulatory Needs and Challenges 229
17.2.1.1 Interests and Values Concerned 229
17.2.1.2 Some of the Challenges 229
17.2.2 Regulatory Tools and Strategies Applied 230
17.2.2.1 Public International Law 231
17.2.2.2 EU Regulation 231
17.2.2.3 Domestic Law 231
17.2.3 Conclusions 233
17.3 Relationship Between Ethics and Legal Regulation 234
17.4 Recommendations of the CHIMBRIDS Project 235
References 237
Part IV Stem Cell Banking for Translational Stem CellResearch or Stem Cell-Based Therapies 238
Chapter 18: Stem Cell Banks: Reality, Roles and Challenges 239
18.1 Introduction and Historical Perspectives on Collectionsof Biological Cultures 240
18.2 What Is a Stem Cell bank? 240
18.3 “Quality?” 243
18.4 Models for Provision of Stem Cell Lines 244
18.5 Benefits of Stem Cell Banks 244
18.6 Assuring Appropriate Procurement of Cell Lines 245
18.7 Standardization of the Banking Process and Good Cell Culture Practice 246
18.8 Challenges for Appropriate Supply of Stem Cell Lines 247
18.9 International Coordination and the Future 248
18.10 Appendix 1. Strategic Aims of the UK Stem Cell Bank 249
References 249
Chapter 19: Broad Consent 251
19.1 Introduction 251
19.2 Broad Consent in Perspective 252
19.3 Morally Justifying Informed Consent Procedures: Three Steps 254
19.4 The Moral Foundation(s) of Informed Consent 256
19.4.1 Protection Against Harm 256
19.4.2 Promoting Autonomy 257
19.4.3 Promoting Trust in Science 257
19.4.4 Beyond Utility: Deontological Constraints and More 257
19.5 Implications 259
19.5.1 Broad Consent as Protection Against Harm 259
19.5.2 Broad Consent and Autonomy 259
19.5.3 Broad Consent and Trust in Science 260
19.5.4 Can Broad Consent Lift Deontological Constraints? 260
19.6 Further Implications 262
19.7 Concluding Remarks 263
References 264
Chapter 20: Banks, Repositories and Registries of Stem Cell Lines: The Challenges to Legal Regulation 265
20.1 Introduction 266
20.2 Why Regulate Collections of Stem Cells? 267
20.3 What Interests Should Regulation Protect? 268
20.4 Research or Treatment – Does It Make a Difference? 269
20.5 International Regulation of Stem Cell Banks 270
20.5.1 Introduction 270
20.5.2 Balancing Consideration for the Individual and Consideration for Research and the Interests of Society 271
20.5.3 Respect for the Self-determination of the Individual 272
20.5.4 Protection of Privacy 274
20.6 Translational Research 275
20.7 Conclusion 276
References 277
Part V Translational Stem Cell Research and Commercial Funding 279
Chapter 21: Proprietary Interests and Collaboration in Stem Cell Science: Avoiding Anticommons, Countering Canalyzation* 280
21.1 Introduction 281
21.2 Property Layers 282
21.2.1 Stem Cell Data 283
21.2.2 Stem Cell Materials 284
21.2.3 Stem Cell Patents 285
21.3 Crowding Out Collaboration? The Tragedy of the Anticommons Versus Patent Canalyzation 285
21.4 Two Models of Stem Cell Commercialization 289
21.4.1 Cancer Stem Cell Consortium 289
21.4.2 Stem Cells for Safer Medicines 290
21.4.3 Managing (Potential) Transaction Costs 291
21.4.4 Minimizing (Potential) Costs to Research Quality 293
21.5 Conclusion 294
References 295
Part VI Patenting of Human Stem Cell-based Inventions:Scientific, Ethical and Regulatory Issues 298
Chapter 22: Legal Problems Raised by Patents on Human Stem Cell-Based Inventions 299
22.1 Introduction 300
22.2 Novelty 301
22.3 Inventive Step 301
22.4 Capable of Industrial Application 302
22.5 Insufficiency 307
22.6 Excluded Subject Matter and Morality 309
22.6.1 No Common Standard of Morality 309
22.6.2 Extreme Approaches 310
22.6.3 A Preferred, but Still Extreme, Solution 310
22.6.4 The Ideal Solution – Pushing It One Bit Further 312
22.6.5 The Test Case: WARF Before the Enlarged Board of Appeal 313
22.6.5.1 The Meaning of Use and Research 313
22.6.5.2 The Meaning of the Term “Embryo” 314
22.6.5.3 The Definition of “Use of the Embryo” 315
22.6.5.4 Industrial or Commercial Purposes 316
22.7 Conclusion 317
References 318
Chapter 23: Patenting of Human Stem Cell-Based Inventions: Can There be Technological Solutions to a Moral Dilemma? 320
23.1 Introduction 321
23.2 The Legal Framework for Patentability 321
23.3 The Definition of the Term “Human Embryo” and Its Implications for Patentability 323
23.4 The European Patent Office’s Position So Far 325
23.5 Technological Alternatives for the Procurement of Human ES Cells 325
23.5.1 Alternatives Involving Non-viable Entities 325
23.5.1.1 Triploid Embryos 325
23.5.1.2 Arrested Embryos 326
23.5.1.3 Nuclear Transfer Embryos Incapable of Implantation 327
23.5.1.4 Parthenotes 328
23.5.2 Alternatives Not Involving the Destruction of the Human Embryo 329
23.6 Outlook and Conclusions 330
References 331
Chapter 24: Patenting of Human Stem Cell-Based Inventions: Ethical Issues Including and Beyond the Morality Clause 333
24.1 Introduction 333
24.2 Ethics: Preliminaries 334
24.3 Ethics and Patents 336
24.3.1 Ethics Before the Application Is Granted 337
24.3.2 Ethics in Patent Law: The Morality Clause 338
24.3.3 Ethics After Patents Have Been Granted 338
24.4 Patents, Economy and Politics 339
24.5 Some Current Criticisms of Patents and Patent Law 339
24.6 Future Relations Between Ethics and Patent Law 341
24.7 A Closer Look at Ethics 341
24.8 Definition and Interpretation Problems 344
24.9 EPO and EGE 345
24.9.1 A Proposal 345
24.9.2 Different Levels 346
24.9.3 Possible Objections 346
24.9.4 Some Advantages 347
24.10 Concluding Remark 347
References 348
Part VII From General Public to Researchers, and Vice Versa:Communication Issues in Translational Stem Cell Research 349
Chapter 25: Ethical, Legal and Social Implicationsof Translational Stem Cell Research: Effectsof Commercialization on Public Opinionand Trust of Stem Cell Research 350
25.1 Introduction 350
25.2 A Primer on Stem Cell Research 351
25.3 Trends in Public Opinion 354
25.3.1 Public Support of or Opposition to SCR 355
25.3.2 Awareness or Knowledge of SCR 358
25.3.3 Perceptions of the Regulatory Environment 359
25.4 Public Trust and Research Commercialization in the SCR Context 360
25.4.1 Stem Cell Research and Commercialization 361
25.4.2 Public Opinion regarding Commercialization and Impact on Public Trust 364
25.5 Conclusion 366
References 368
Chapter 26: Patients’ Organizations and Their Opinions: How Much Have They Been Taken into Consideration When Regulating Stem Cell Research? 373
26.1 Introduction 374
26.2 The Patient Advocacy Movement: A Brief Historyand Successes to Date 375
26.3 The Role of Patient Advocacy in TranslationalStem Cell Research 377
26.4 Conclusions 380
References 381
Chapter 27: Communicating Translational Stem Cell Research to the General Public: Challengesand Suggestions 382
27.1 Introduction 382
27.2 Background of Science–Society Interactions 383
27.3 A Controversial Field 384
27.4 Secure a Scientist’s Support 385
27.5 Outreach and Academia 386
27.5.1 Outreach Needs Academics 386
27.5.2 Interest in Science Versus Neutrality 388
27.6 Whom Should We Educate? 389
27.7 Breaking Self-sustained Debates 390
27.8 A Matter of Duty 391
27.8.1 A Scientist’s Duty 391
27.8.2 Freedom of Choice 392
27.8.3 Legal Dimension of the Debate 392
27.9 Dealing with Lobbies 393
27.10 Keep It Simple 394
27.11 Conclusion 394
References 395
Part VIII Translational Stem Cell Research and Its PsychologicalImplications 396
Chapter 28: Psychosocial and Cultural Factors Affecting Judgments and Decisions About Translational Stem-Cell Research 397
28.1 Introduction 397
28.2 Intuitive Understandings of Risk 398
28.3 Worldviews and Values 399
28.4 How Value Predispositions and Knowledge Interact 400
28.5 Cultural Differences in Decision Processes 401
28.6 Diffusion of Innovations Through Social Networks 402
28.7 Recommendations for Policymakers 403
28.8 Conclusion 404
References 404
Part IX Ethical Evaluation of Translational Stem Cell ResearchProjects in Research Ethics Committees 406
Chapter 29: Ethics and Uncertainty: Considerations for the Design and Review of Translational Trials Involving Stem Cells 407
29.1 Introduction 407
29.2 The Challenges: An Overview 408
29.3 Assessment of Risk 409
29.4 Assessment of Direct-Benefit 410
29.5 Assessment of Social Value 411
29.6 Assessment of Favorable Risk-Benefit Value 412
29.7 Design and Evaluation of Preclinical and FIH Studies 414
29.8 Subject Selection 414
29.9 Justice 415
29.10 Informed Consent 416
29.11 Privacy and the Procurement of Stem Cell Tissues 417
29.12 Independent Review 418
29.13 Conclusion 418
Note 419
References 420
Part X Looking at the Future of Translational Stem CellResearch and Stem Cell-Based Therapeutic Applications:Risks, Long-Term Effects and Priority Setting 423
Chapter 30: Unruhe und Ungewissheit: Stem Cellsand Risks1 424
30.1 Introduction 424
30.2 Stem Cells: Some Risks and Benefits 425
30.3 Why Risk Analysis? 428
30.4 Types of Decision 428
30.5 Time: Pushing and Tugging 430
References 432
Chapter 31: Looking at the Future of TranslationalStem Cell Research and Stem Cell-basedTherapeutic Applications: Priority Settingand Social Justice 433
31.1 Introduction 434
31.2 Setting Research Priorities 434
31.3 Setting Priorities in Health Care 435
31.4 Two Perspectives 436
31.5 New and Different Standards? 437
31.6 Priority-Setting and the Health Care Systems 438
31.7 General Normative Points of Departure 439
31.8 Some Relevant Variables or Dimensions 440
31.9 Medical Tourism, Risks and Ethics 441
31.10 Problems of Uncertainties and Knowledge Gaps 442
31.11 Cases of Increasing Difficulty 443
31.12 A Diagram 445
31.13 More on the Role of Values and Norms 446
31.14 Social Justice Aspects 447
31.15 Concluding Remark 448
References 449
Index 450

Produkt-Details

• Erscheint lt. Verlag: 25.12.2010
• Reihe/Serie: Stem Cell Biology and Regenerative Medicine
• Reihe/Serie: Stem Cell Biology and Regenerative Medicine
• Zusatzinfo: XXVI, 462 p.
• Verlagsort: Totowa
• Sprache: englisch
• Themenwelt: Studium ► 1. Studienabschnitt (Vorklinik) ► Biochemie / Molekularbiologie
• Themenwelt: Naturwissenschaften ► Biologie ► Genetik / Molekularbiologie
• Themenwelt: Technik
• Schlagworte: ethical stem cell research • TRANSLATIONAL STEM CELL RESEARCH
• ISBN-10: 1-60761-959-8 / 1607619598
• ISBN-13: 978-1-60761-959-8 / 9781607619598