Cellular Transplants: From Lab to Clinic provides a thorough foundation of the basic science underpinning this exciting field, expert overviews of the state-of-the-art, and detailed description of clinical success stories to date, as well as insights into the road ahead. As highlighted by this timely and authoritative survey, scale-up technologies and whole organ transplantation are among the hurdles representing the next frontier.
The contents are organized into four main sections, with the first covering basic biology, including transplant immunology, the use of immunosuppressive drugs, stem cell biology, and the development of donor animals for transplantation. The next part looks at peripheral and reconstructive applications, followed by a section devoted to transplantation for diseases of the central nervous system. The last part presents efforts to address the key challenges ahead, such as identifying novel transplantable cells and integrating biomaterials and nanotechnology with cell matrices.
? Provides detailed description of clinical trials in cell transplantation
? Review of current therapeutic approaches
? Coverage of the broad range of diseases addressed by cell therapeutics
? Discussion of stem cell biology and its role in transplantation
There have been tremendous strides in cellular transplantation in recent years, leading to accepted practice for the treatment of certain diseases, and use for many others in trial phases. The long history of cellular transplantation, or the transfer of cells from one organism or region of the body to another, has been revolutionized by advances in stem cell research, as well as developments in gene therapy. Cellular Transplants: From Lab to Clinic provides a thorough foundation of the basic science underpinning this exciting field, expert overviews of the state-of-the-art, and detailed description of clinical success stories to date, as well as insights into the road ahead. As highlighted by this timely and authoritative survey, scale-up technologies and whole organ transplantation are among the hurdles representing the next frontier. The contents are organized into four main sections, with the first covering basic biology, including transplant immunology, the use of immunosuppressive drugs, stem cell biology, and the development of donor animals for transplantation. The next part looks at peripheral and reconstructive applications, followed by a section devoted to transplantation for diseases of the central nervous system. The last part presents efforts to address the key challenges ahead, such as identifying novel transplantable cells and integrating biomaterials and nanotechnology with cell matrices. Provides detailed description of clinical trials in cell transplantation Review of current therapeutic approaches Coverage of the broad range of diseases addressed by cell therapeutics Discussion of stem cell biology and its role in transplantation
Front cover 1
Cellular Transplantation 4
Copyright page 5
Table of contents 6
Contributors 8
Preface 14
Part A: The Basic Biology of Cell Therapy 16
Chapter 1. Immunology of Cell and Tissue Xenotransplantation 18
Introduction 18
The Rationale for Xenotransplantation 19
Source of Xenografts 19
The Immunological Barriers to Xenotransplantation: An Overview 20
The Type of Transplant and the Barrier to Xenotransplantation 20
The Immune Response to Cell and Tissue Transplants 20
B-cells, Antibodies, and the Barrier to Cell and Tissue Transplantation 23
Therapeutic Approaches to Cell and Tissue Transplantation 24
Acknowledgments 24
Chapter 2. Current Immunosuppressive Drugs and Clinical Use 28
The Alloimmune Response 28
Azathioprine 29
Cyclosporine 29
Tacrolimus 31
Sirolimus 32
Mycophenolate Mofetil 33
Corticosteroids 34
Protein Drugs 35
Polyclonal Antilymphocyte Sera 35
Monoclonal Antibody Preparations 36
Anti-CD-20 38
Alemtuzumab 38
Co-stimulation Inhibitors 38
Deoxyspergualin 39
Conclusions 39
Chapter 3. Stem and Precursor Cells for Transplant Therapy 44
Introduction 44
Some Basic Facts 44
Cell Source Issues 45
Difficulties Researchers Face 51
Future Prospects 52
Chapter 4. Creating Animals for Cell Xenotransplantation 58
The Development of Microinjection 58
Embryonic Stem Cells and Knockouts 58
Dolly the Sheep and Other Animals 59
Making Pigs 60
Regulators of Complement Activation (RCA) 61
Inhibition of Complement Activation in Xenotransplantation 61
Pigs Transgenic for Complement Regulatory Proteins 62
Islet Xenotransplantation 63
Clinical Islet Xenotransplantation 65
Clinical Neural Xenotransplantation 66
Other Transgenic Pigs Generated for Xenotransplantation 66
Conclusions and Future Directions 67
Part B: Cell Therapy for Peripheral Diseases and Reconstructive Applications 72
Chapter 5. Islet Transplants for Diabetes: The Edmonton Protocol 74
Introduction 74
Historical Perspectives on Islet Transplantation 76
Current Clinical Islet Transplantation 78
Inefficiency of Islet Isolation and Transplantation 80
Clinical Islet Transplantation 80
Why the Liver? 84
Peritransplant Glucose Management 84
Posttransplant Monitoring 85
Assessment of Islet Function 85
Outcomes 86
Insulin Independence 86
Insulin Secretion and Blood Glucose Control 87
Hypoglycemia and Glycemic Lability 87
Microvascular Complications 88
Cardiovascular Disease 89
Risks of Islet Transplantation 90
Summary 91
Other Transplant Settings 91
Future Directions 92
Chapter 6. Characterization of Islet Preparations 100
Introduction 100
Islet Isolation 101
What Do We Want to Know? 103
Islet Purity and Cell Composition 103
Viability 121
Postscript 139
Acknowledgments 139
List of Symbols 139
Chapter 7. Encapsulated Human Islet Allografts: Providing Safety with Efficacy Providing Safety with Efficacy 150
Restrictions Preventing Wide Acceptance of Clinical Islet Transplantation with Immunosuppression 150
Complications Related to Immunosuppression 151
Cartoon Descriptions of Encapsulated Cell Therapy Immune Protection 151
Development of Encapsulated Islet Transplantation 154
Clinical Trials of Encapsulated Human Islets 158
Novocell PEG Encapsulation Technology 158
Chapter 8. Strategies for Cell Replacement for Kidney Failure 170
Introduction 170
Integration of New Nephrons into the Kidney 171
Organogenesis 173
Isotransplantation/Allotransplantation of Embryonic Kidneys to Enhance Renal Function 174
Availability of Source Material for Renal Anlage Transplants 176
Xenotransplantation of Embryonic Kidneys 177
Stem Cells 179
Generation of Histocompatible Tissues Using Nuclear Transplantation/Therapeutic Cloning 180
Perspectives and Challenges 181
Chapter 9. Strategies for Extracorporeal Devices for Kidney Failure 184
Introduction 184
Normal Kidney Function 184
Current Status of Renal Support 186
Cell Therapy and Tissue Engineering Approach to Renal Replacement Therapy 187
Engineering a Bioartificial Kidney 187
Implantable Bioartificial Kidney 191
Extracorporeal Bioartificial Kidney 192
Summary 198
Disclosures 198
Acknowledgements 198
Chapter 10. Transplants for Hemophilia 202
Hemophilia 202
Stem Cell Transplantation in Hemophilia 204
Human Keratinocytes 205
Fibroblasts 206
Hepatocytes 207
Myocytes 208
Endothelial Cells 209
Vector Choice and Design of Gene Expression 209
Mechanisms to Prevent Immune-Mediated Rejection of Cell Transplant for the Treatment of Hemophilias 211
Encapsulation 212
Ahead Looking 212
Chapter 11. Cell Therapy for Peripheral Diseases and Reconstructive Applications: Transplants for Lysosomal Storage Disease 220
Background 220
BMT 221
Other Cell-based Therapies for LSD 222
Organ Transplantation 225
Conclusions 226
Chapter 12. Cellular Transplants for Liver Diseases 230
Introduction 230
Liver Organization, Function, and Disease 231
Cell Types 234
Discussion: Current Cell-based Transplants for Liver Disease 237
Immune Response Modulation and Tolerance 248
Conclusions and Future Directions 249
Chapter 13. Stem Cell Transplantation for Autoimmune Diseases 256
Introduction 256
Autoimmune Disease 256
Phase I/II Studies 258
Other Issues 262
Mesenchymal Stem Cell 263
Immunomodulation of Autoimmune Disease 263
Conclusions 266
Acknowledgments 267
Chapter 14. Cardiac Cell Transplantation 274
Background 274
Contractile Cells 275
Noncontractile Cells 277
Clinical Studies 281
Challenges for Future Improvement 283
Conclusions 285
Chapter 15. Cylindrical Cartilage Transplantation for Tracheal Replacement 290
Introduction 290
Cylindrical Tube: Comparison of Tracheal and Nasal Chondrocytes 291
Cylindrical Tube: Composite Chondrocyte and Epithelial Cells 294
Helical and Y-Shape (Carina) 295
Autologous Engineered Trachea 297
Marrow Stromal Cells with TGF-b2 Released from Biodegradable Microspheres by pouring 20 µl of 100 mM phosphate-buffered saline 299
Discussion 300
Chapter 16. Muscle Cell Transplants 304
Introduction 304
Duchenne’s Muscular Dystrophy 304
Postnatal (Adult-derived) Stem Cell Therapy 308
Other Therapeutic Applications of MDSCs 309
Conclusions 312
Acknowledgments 312
Part C: Cell Therapy for CNS Diseases 318
Chapter 17. Immunological Considerations in CNS Transplants 320
Introduction 320
CNS Immunology and Its Immune Privilege 320
Transplantation to the CNS and the Mechanisms of Graft Rejection 324
Strategies for Overcoming Graft Rejection in the CNS 331
Acknowledgments 335
Summary 335
Chapter 18. Neurotrophic Cell Transplants for Degenerative Diseases of the Eye 342
Introduction 342
Anatomy of the Eye 342
Cell Encapsulation for Immunoisolation 343
Cell Encapsulation Engineering 345
Neurotrophic Factors in the Eye 346
Ciliary Neurotrophic Factor (CNTF) 347
Brain-derived Neurotrophic Factor 348
Glial-cell-line-derived Neurotrophic Factor (GDNF) 349
Other Neurotrophic Factors 350
Neurotrophic Encapsulated Cell Therapy: Proof of Principle in the CNS 351
Clinical Trials: Cell Therapy in the Eye 352
Conclusions 354
Chapter 19. Transplants for Glioblastoma 360
Introduction 360
Animal Models 360
New Treatment Principles for Gliomas 361
Stem Cell Therapy 362
Cell-based Delivery Systems 363
Future Prospects 364
Chapter 20. NT2N Cell Transplantation and GDNF Treatment in Stroke: Linking Neurotrophic Factor Therapy and Neuroprotection 368
Acknowledgments 368
The Regenerative Stroke Brain 368
Initial Cell Transplantation Studies Using Fetal Tissues 369
NT2N Cells: Cancer Cells Turned Neuronal Cells 369
Normal Host Brain Microenvironment and NT2N Cell Grafts 370
Stroke Host Brain Microenvironment and NT2N Cell Grafts 371
Preclinical Studies of NT2N Cell Grafts in Stroke 371
Immunosuppression and NT2N Cell Grafts 373
Neurotrophic Factors Influencing Therapeutic Benefits of NT2N Cell Grafts 374
Clinical Trials of NT2N Cells in Stroke Patients 375
Recent Advances on the Use of NT2N Cells for Transplantation Therapy 376
NT2N Cells and Gene Therapy 377
Glial-cell-line-derived Neurotrophic Factor 378
GDNF Protein Delivery into the Brain 379
Viral Vectors for GDNF Gene Therapy 379
Limitations of the Viral Vector Strategy for GDNF Therapy 380
Stroke Pathology as Guide for Optimizing GDNF Therapy 381
Combined NT2N Cell Transplantation and GDNF Therapy 381
Chapter 21. NGF-producing Cell Transplants for Alzheimer’s Disease 388
The Septo-hippocampal, NGF-dependent Cholinergic System in Alzheimer’s Disease and Animal Models 388
Brain Tissue Grafts Lending Trophic Support to the Host Brain or to Adjacent Grafts 390
Peripheral Tissue Grafts Lending Trophic Support to Host Brain or Adjacent Grafts 392
Engineered Cells or Biomaterials That Produce NGF 392
Clinical Applications 394
Past Concerns and Future Promise for NGF Therapy in the Alzheimer Patient 395
Acknowledgments 396
Chapter 22. Transplants of CNTF-producing Cells for the Treatment of Huntington’s Disease 400
Introduction 400
Huntington’s Disease 400
Therapeutic Strategies for Huntington’s Disease 402
Ciliary Neurotrophic Factor (CNTF) 403
Cellular Vectors for CNTF Delivery in HD 405
Clinical Phase I Trial for Encapsulated Cells in HD 407
Conclusions 409
Chapter 23. Choroid Plexus Epithelial Cell Transplants for Repair of the Brain 414
Introduction 414
Basic Structure of the Choroid Plexus 414
Traditional Roles of the Choroid Plexus 416
Choroid Plexus as a First Line of Defense for the Brain 416
Central Secretory Role of the Choroid Nerve growth factor Plexus in Brain Function 417
The Choroid Plexus in CNS Early Development 417
Choroid Plexus and Neurodegeneration: Alzheimer’s Disease and Ischemia as Examples 419
Choroid Plexus and Neurogenesis 420
Harnessing the Choroid Plexus for Transplantation Therapy: Preliminary Studies 421
Immunoisolation within Alginate Microcapsules Enables the Use of Xenogeneic Choroid Plexus Transplants 421
Characterization of Alginate and Encapsulated Choroidal Epithelial Cells 422
Encapsulated Xenogeneic Choroid Plexus Transplants in Animal Models of Stroke 423
Encapsulated Xenogeneic Choroid Plexus Transplants in a Rat Model of Huntington’s Disease 424
Encapsulated Xenogeneic Choroid Plexus Transplants in a Monkey Model of Huntington’s Disease 425
Conclusions 426
Chapter 24. Neural Transplantation in Huntington’s Disease 432
Huntington’s Disease 432
Functional Animal Models 433
Functional Experimental Transplants 435
Clinical Trials 438
Side Effects and Outstanding Issues 442
Summary and Future Prospects 444
Acknowledgments 445
Chapter 25. Neural Transplantation in Parkinson’s Disease 454
Parkinson’s Disease 454
Functional Animal Models 455
Functional Experimental Transplants 456
Clinical Trials 459
Side Effects and Problems 460
Acknowledgments 464
Chapter 26. Transplants for Chronic Pain 470
Introduction 470
Cellular Replacement Strategies in the Management of Chronic Pain 470
Adrenal Medullary Chromaffin Cells for Analgesic Delivery 472
Cellular Pump Strategies in the Management of Chronic Pain 472
Preclinical Studies Using Adrenal Medullary Transplants in Pain Models 473
Adrenal Medullary Transplants in Acute Pain 473
Adrenal Medullary Transplants in Chronic Pain: Potential Mechanisms 473
Adrenal Medullary Transplants in Chronic Pain of Differing Etiologies 475
Clinical Trials Using Adrenal Medullary or Chromaffin Cell Transplants for Chronic Pain 475
Cell Lines for Analgesic Delivery 478
Chromaffin Cells Revisited 480
Chapter 27. Cell Grafting for Spinal Cord Injury Repair: Cell Replacement and Bridging Strategies 492
Acknowledgments 492
Introduction 492
Spinal Cord Injury Epidemiology and Pathophysiology 492
Repairing the Injured Spinal Cord 494
Cell Grafting for SCI Repair 496
Chapter 28. Human Embryonic Stem Cells, Dopaminergic Neurons, and Pathways for Developing a Parkinson’s Disease Therapy 538
Acknowledgments 538
Introduction 538
“Traditional” Transplantation Using Fetal Cells 538
Clinical Studies 540
Why We Need Cultured Cells 541
Stem Cells and Cells at Other Stages of Development 542
Development of Dopaminergic Neurons 542
Dopamine Neurons from Neural Stem Cells and Other Sources 543
Mouse and Subhuman Primate Embryonic Stem Cells 545
Human Embryonic Stem Cells (hESC) 545
Genetic and Epigenetic Stability 546
An Alternative to hESCs: NTera2 547
Designer Stem Cells 548
Beyond Stem Cells: Cell Lines and Other Possibilities 549
Engineering Stem Cells 550
Conclusions 551
Part D: Future Avenues of Cell Therapy 560
Chapter 29. Concepts in Cell Therapy: From Cord Blood to Sertoli Cells 562
Introduction 562
Cord Blood Transplants 563
Cord Blood Hematopoietic Stem Cells (HSCs) 563
Cord Blood Mesenchymal Stem Cells (MSCs) 564
Cord Blood Endothelial Progenitor Cells (EPCs) 565
Cord Blood Neural Progenitor Cells 566
Cord Blood Therapy for Acute Ischemic Diseases 567
Cord Blood Cells for Neurological Diseases 570
Cord Blood as a Treatment for Inborn Errors of Metabolism with Neurologic Consequences 570
Cord Blood Therapies for Neurodegenerative Diseases 571
Therapeutic Potential of Blood-derived Cells 572
Sertoli Cells and Transplantation Tolerance 572
Future Directions in Stem Cell Therapy 574
Chapter 30. Immunologically Privileged Environments 582
Acknowledgments 582
Background: What Is “Immunological Privilege”? 582
Immunologically Privileged Tissues: The Evidence 583
Unifying Principles: Mechanisms v 588
Relevance of Immunological Privilege to Transplantation Medicine 594
Chapter 31. Converging Cell Therapy with Biomaterials 606
Introduction 606
The Immune Response to Biomaterials 607
Biomaterial Design 608
Promoting Therapeutic Immune Responses 613
Conclusions and Future Directions 617
Chapter 32. Nanotechnology’s Impact on Cell Transplantation 626
Introduction 626
Cell Biology Nanoscale: What’s the Big Deal? 626
Mechanical Influences 627
Contact Guidance 627
Self-assembled Nanostructures 627
Drug and Gene Delivery 628
Nanoparticles for Screening and Monitoring of Transplanted Tissue 630
Tissue Engineering 632
Cellular Immunoisolation 633
Cell Encapsulation Conclusion 637
Future of Nanotechnology 638
Chapter 33. Design and Implementation of a Cell Processing Facility 644
Introduction 644
Clean Room Construction 644
Biological Safety Cabinet 645
Selection of Furniture 645
Change Room 645
Microbiological Monitoring in Controlled Environments 645
Regulation 647
Islet Isolation Facility at the University of Alberta 647
Conclusions 648
Chapter 34. Developing Cell Therapy Products 650
Introduction 650
Product Development 650
Organizational Life Cycles 651
Technology Transfer 652
Product Definition 652
Product Development Plan and Budget 653
Intellectual Property 657
Product Development Tools 658
Window of Opportunity 660
Index 662
Contributors
The number in parentheses indicates the chapter to which the author contributed.
Karen S. Aboody(19)
The Divisions of Hematology/Hematopoietic Cell Transplantation and Neurosciences, City of Hope National Medical Center and Beckman Research Institute, Duarte, California
Omar A. Ali(31)
Division of Engineering and Applied Sciences, Harvard University, Cambridge, Massachusetts
Rose Amable(28)
Development and Plasticity Section, Cellular Neurobiology Research Branch, Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, Department of Health and Human Services, Baltimore, Maryland
D.J. Barakat(27)
The Miami Project to Cure Paralysis, Department of Neurological Surgery, University of Miami School of Medicine, Miami, Florida
Rolf Bjerkvig(19)
NorLux Neuro-Oncology, Department of Biomedicine, University of Bergen, Norway and NorLux Neuro-Oncology, Centre Recherche Public Santé, Luxembourg
Katarina Le Blanc(13)
Dept of Allogeneic Stem Cell Transplantation, Karolinska Institute, Stockholm, Sweden
Susan Bonner-Weir(6)
Section on Islet Transplantation and Cell Biology, Joslin Diabetes Center, Harvard Medical School, Boston, Massachusetts
Cesario V. Borlongan(20)
Research and Affiliations Service Line, Augusta VAMC, Augusta, Georgia
Department of Neurology and Institute of Molecular Medicine and Genetics, Medical College of Georgia, Augusta, GA
Justin M. Burns(2)
Division of Transplantation Surgery, Carolinas Medical Center, Charlotte, North Carolina
Jingli Cai(3)
National Institute on Aging, Triad Technology Center, Baltimore, Maryland
Don F. Cameron(29)
Center for Excellence for Aging and Brain Repair, Department of Anatomy, USF Health, Tampa, Florida
Vince P. Casingal(2)
Division of Transplantation Surgery, Carolinas Medical Center, Charlotte, North Carolina
Daniel A. Castellanos(26)
Miami Project to Cure Paralysis, University of Miami Miller School of Medicine, Miami, Florida
Clark K. Colton(6)
Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts
Bryce H. Davis(14)
Duke University, Department of Biomedical Engineering, Durham, North Carolina
Nicole Déglon(22)
Atomic Energy Commission, CEA CNRS URA 2210 Unit and MiRcen ImaGene Program
Nagwa S. El-Badri(29)
Center for Excellence for Aging and Brain Repair, Department of Neurosurgery, USF Health, Tampa, Florida
Per Oyvind Enger(19)
NorLux Neuro-Oncology, Department of Biomedicine, University of Bergen, Norway and NorLux Neuro-Oncology, Centre Recherche Public Santé, Luxembourg
Denis K. English(29)
Center for Excellence for Aging and Brain Repair, Departments of Neurosurgery, USF Health, Tampa, Florida
Carole Escartin(22)
Atomic Energy Commission, CEA CNRS URA 2210 Unit and MiRcen ImaGene Program
Yoshikatsu Eto(11)
Department of Gene Therapy, Institute of DNA Medicine, Department of Pediatrics, The Jikei University School of Medicine, Tokyo, Japan
William J. Freed(28)
Development and Plasticity Section, Cellular Neurobiology Research Branch, Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, Department of Health and Human Services, Baltimore, Maryland
Shyam Gajavelli(26)
Miami Project to Cure Paralysis, University of Miami Miller School of Medicine, Miami, Florida
Svitlana Garbuzova-Davis(29)
Center for Excellence for Aging and Brain Repair, Department of Neurosurgery, USF Health, Tampa, Florida
Andrew Gómez-Vargas(10)
Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario, Canada
Paul F. Gores(2)
Division of Transplantation Surgery, Carolinas Medical Center, Charlotte, North Carolina
Ann-Charlotte Granholm(21)
Department of Neurosciences and the Center on Aging, Medical University of South Carolina, Charleston, South Carolina
Amal Hakki(29)
Center for Excellence for Aging and Brain Repair, Department of Neurosurgery, USF Health, Tampa, Florida
Craig Halberstadt(32)
Carolinas Medical Center, Charlotte, North Carolina
Marc R. Hammerman(8)
Renal Division, Departments of Medicine, and Cell Biology and Physiology, Washington, University School of Medicine, St. Louis, Missouri
Philippe Hantraye(22)
Atomic Energy Commission, CEA CNRS URA 2210 Unit and MiRcen ImaGene Program Isotopic Imaging, Biochemical and Pharmacological Unit, Service Hospitalier Frederic Joliot, CEA, Orsay, France
Koichi Hara(20)
Research and Affiliations Service Line, Augusta VAMC, Augusta, Georgia
Mark P. Hedger(30)
Monash Institute of Medical Research, Monash University, Melbourne, Australia
Robert Henning(29)
Center for Excellence for Aging and Brain Repair, Department of Internal Medicine, USF Health, Tampa, Florida
David C. Hess(20)
Research and Affiliations Service Line, Augusta VAMC, Augusta, Georgia
Department of Neurology and Institute of Molecular Medicine and Genetics, Medical College of Georgia, Augusta, GA
Gonzalo Hortelano(10)
Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario, Canada Research and Development, Canadian Blood Services
Johnny Huard(16)
Department of Bioengineering, University of Pittsburgh
Growth and Development Laboratory, Children’s Hospital of Pittsburgh
Departments of Orthopaedic Surgery and Molecular Genetics and Biochemistry, University of Pittsburgh
David H. Humes(9)
Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, Michigan
Tatsuya Kin(33)
Clinical Islet Transplant Program, University of Alberta and Capital Health Authority, Edmonton, Alberta, Canada
Stephen K. Klasko(29)
Center for Excellence for Aging and Brain Repair, University of South Florida College of Medicine, USF Health, Tampa, Florida
Koji Kojima(15)
Laboratory for Tissue Engineering and Regenerative Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts
Nicholas J. Krebs(12)
The Center for Regenerative Medicine, Massachusetts General Hospital
Jonathan R.T. Lakey(33)
Clinical Islet Transplant Program, University of Alberta and Capital Health Authority, Edmonton, Alberta, Canada
Mitra Lavasani(16)
Department of Bioengineering, University of Pittsburgh Growth and Development Laboratory, Children’s Hospital of Pittsburgh
Chun-Ting Lee(28)
Development and Plasticity Section, Cellular Neurobiology Research Branch, Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, Department of Health and Human Services, Baltimore, Maryland
Noriyuki Matsukawa(20)
Research and Affiliations Service Line, Augusta VAMC, Augusta, Georgia
Mohammadreza Mirbolooki(33)
Clinical Islet Transplant Program, University of Alberta and Capital Health Authority, Edmonton, Alberta, Canada
David J. Mooney(31)
Division of Engineering and Applied Sciences, Harvard University, Cambridge, Massachusetts
Craig Neville(12)
The Center for Regenerative Medicine, Massachusetts General Hospital
Department of Pediatric Surgery, Mass General Hospital for Children and Harvard Medical School
Toya Ohashi(11)
Department of Gene Therapy, Institute of DNA Medicine, Department of Pediatrics, The Jikei University School of Medicine, Tokyo, Japan
Abdulkadir Omer(6)
Section on Islet Transplantation and Cell Biology, Joslin Diabetes Center, Harvard Medical School, Boston, Massachusetts
Jack J. O’Neil(6)
Section on Islet Transplantation and Cell Biology, Joslin Diabetes Center, Harvard Medical School, Boston, Massachusetts
Lifescan, Inc., Johnson and Johnson, Skillman, New...
| Erscheint lt. Verlag | 10.10.2011 |
|---|---|
| Sprache | englisch |
| Themenwelt | Sachbuch/Ratgeber |
| Medizin / Pharmazie ► Medizinische Fachgebiete ► Chirurgie | |
| Medizin / Pharmazie ► Medizinische Fachgebiete ► Neurologie | |
| Medizin / Pharmazie ► Physiotherapie / Ergotherapie ► Orthopädie | |
| Studium ► 1. Studienabschnitt (Vorklinik) ► Histologie / Embryologie | |
| Naturwissenschaften ► Biologie ► Zellbiologie | |
| Technik ► Medizintechnik | |
| Technik ► Umwelttechnik / Biotechnologie | |
| ISBN-10 | 0-08-046904-3 / 0080469043 |
| ISBN-13 | 978-0-08-046904-1 / 9780080469041 |
| Haben Sie eine Frage zum Produkt? |
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