Contributors xi
Introduction xv
1 AMNIOTIC FLUID STEM CELLS 1
Sean Vincent Murphy and Anthony Atala
Introduction 1
Development of Gestational Stem Cells 2
Isolation and Characterization of Amniotic Fluid Stem Cells 2
Multipotency of Amniotic Fluid Stem Cells 3
Clinical Application of Amniotic Fluid Stem Cells 8
Conclusion 13
References 13
2 CORD BLOOD TRANSPLANTS: PERINATAL STEM CELLS IN CLINICAL PRACTICE 17
Richard L. Haspel and Karen K. Ballen
Introduction 17
Hematopoietic Stem Cell Transplants: Adult Donor Collection 17
Hematopoietic Stem Cell Transplants: HLA Matching 18
Collection and Processing of Cord Blood Units 19
Hematopoietic Stem Cell Transplants: Recipient Issues 20
Bone Marrow versus Single Cord Blood: Pediatric 21
Bone Marrow versus Cord Blood: Adults 23
Cord Blood Transplant: Advantages and Disadvantages 23
Double Cord Blood Transplants: Ablative Regimens 24
Double Cord Blood Transplant: Non-Myeloablative Regimens 26
Are Two Cords Better Than One? 27
Chimerism 28
Predicting the Winner 28
Other Experimental Strategies 30
Summary 31
References 31
3 HEMATOPOIETIC STEM CELL DEVELOPMENT IN THE PLACENTA 37
Katrin E.R. Ericson, Akanksha Chhabra, and Hanna K.A. Mikkola
Introduction 37
The Hematopoietic System 37
Historical Perspective on Placental Hematopoiesis 38
The Development and Structure of the Mouse Placenta 39
Hematopoietic Activity in the Mouse Placenta 40
Identification of Placental HSCs 42
The Origin and Localization of Placental HSCs 43
Hematopoietic Activity in the Human Placenta 45
Hematopoietic Microenvironment in the Placenta 46
Conclusions and Perspectives 47
References 49
4 PERINATAL MESENCHYMAL STEM CELL BANKING FOR UMBILICAL CORD BLOOD TRANSPLANTATION AND REGENERATIVE MEDICINE 53
Rouzbeh R. Taghizadeh
Introduction 53
Hematopoiesis 54
Hematopoietic Transplantations 54
Umbilical Cord: Source of Perinatal HSCs and MSCs 56
Hematopoietic Transplantations of Umbilical Cord Blood 57
Strategies to Overcome the Transplant-Related Limitations of Umbilical Cord Blood 58
Umbilical Cord Tissue MSC Banking 61
References 63
5 MAKING ORGAN AND STEM CELL TRANSPLANTATION SAFER: THE ROLE OF MESENCHYMAL STEM CELLS 71
Hans Klingemann
Introduction 71
MSC to Prevent Rejection After Solid Organ Transplantation 72
MSC in the Treatment of Graft-versus-Host Disease 73
MSC to Support Hematopoietic Recovery of Stem Cells After Stem Cell Transplantation 74
References 75
6 WHARTONS JELLY MESENCHYMAL STEM CELLS AND IMMUNE MODULATION: REGENERATIVE MEDICINE MEETS TISSUE REPAIR 77
Rita Anzalone, Felicia Farina, Melania Lo Iacono, Simona Corrao, Tiziana Corsello, Giovanni Zummo, and Giampiero La Rocca
Introduction 77
Expression of Relevant Immunomodulatory Molecules in Vitro by MSCs 79
Tolerance Induction by MSCs: Rediscovering the Embryo Immune Evasion Mechanisms 79
Immune Modulation in Vivo: Contrasting Data on the Immune Privilege of MSCs 80
WJ-MSC in in Vivo Models: Enhancing the Immunomodulatory Features of Adult MSC Populations 82
Conclusions and Future Perspectives 83
References 84
7 IMMUNOGENICITY VERSUS IMMUNOMODULATION OF PERINATAL STEM CELLS 89
Bram Lutton and Raimon Duran-Struuck
Introduction 89
Mechanisms of Immunomodulation by Umbilical Cord- and Bone Marrow-Derived MSCs 90
Innate Immune System 90
Adaptive Immune System 92
Natural Tolerance and Umbilical Cord Tissues 94
Tolerance versus Immunogenicity: The Yin and Yang of Host Responses to Umbilical Cord-Derived Cells 95
Conclusions 97
References 98
8 THE TRANSLATIONAL POTENTIAL OF PERINATAL STEM CELLS IN CLINICAL MEDICINE: MESENCHYMAL STEM CELLS 105
Radbeh Torabi, Vincenzo Villani, Christopher A. Mallard, and Curtis L. Cetrulo, Jr.
Introduction 105
Graft-versus-Host Disease 106
Acute GVHD 107
Chronic GVHD 108
GVHD Prevention 109
Hematopoetic Recovery and HCT Engraftment 109
Hematopoietic Recovery 110
HCT Engraftment 111
MSC Potential Uses 111
References 113
9 NEWBORN STEM CELLS: IDENTITY, FUNCTION, AND CLINICAL POTENTIAL 119
Anthony Park, Louis Chan, Mayur Danny I. Gohel, Sean Murphy, Ursula Manuelpillai, Ann Chidgey, and Richard Boyd
Introduction 120
The Newborn Offers an Enormous Opportunity for Stem Cells 120
Amnion 120
Isolation and Phenotypic Characterization of Amnion Cells 121
Therapeutic Potential of Amnion Membrane 123
Mechanisms of AEC-Enhanced Wound Repair 125
Therapeutic Potential of Amnion as Single Cells 127
Amnion Immunogenicity and Immunosuppressive Properties 127
Amnion-Derived Mesenchymal Stromal Cells 128
Umbilical Cord Mesenchymal Stromal Cells 130
Chorion MSCs 131
References 133
10 BIOMEDICAL POTENTIAL OF HUMAN PERINATAL STEM CELLS 139
Oleg V. Semenov and Christian Breymann
Role of Stem Cells in Regenerative Medicine 139
Perinatal Stem Cell Sources 140
Properties of Perinatal Mesenchymal Stem Cells 143
Properties of Perinatal Hematopoietic Stem Cells 144
Biomedical Applications of Human Perinatal Stem Cells 145
Perspectives and Obstacles 147
References 148
11 PROGENITOR CELL THERAPY FOR THE TREATMENT OF TRAUMATIC BRAIN INJURY 155
Alex Bryan Olsen, Robert A. Hetz, Supinder S. Bedi, and Charles S. Cox, Jr.
Introduction 155
Cellular Therapy for the Treatment of TBI 159
Neural Stem Progenitor Cells 159
Human Multipotent Adult Progenitor Cells 160
Mesenchymal Stem Cells 163
Umbilical Cord Blood 165
Whartons Jelly 166
Amniotic Fluid-Derived Stem Cells 167
The Inflammatory Reflex 168
Conclusion 170
References 171
12 THE HUMAN AMNIOTIC MEMBRANE: A TISSUE WITH MULTIFACETED PROPERTIES AND DIFFERENT POTENTIAL CLINICAL APPLICATIONS 177
Maddalena Caruso, Antonietta Silini, and Ornella Parolini
Introduction 177
Structure and Histology of the Human Amniotic Membrane 178
Preparation, Preservation, and Sterilization of the Human Amniotic Membrane 179
Biological and Structural Properties of the Human Amniotic Membrane Generally Invoked to Explain Its Effects in Vivo 180
Established Clinical Applications of the Human Amniotic Membrane 183
Prospective Applications of the Human Amniotic Membrane: Lessons from Preclinical Studies 187
Conclusions and Perspectives 190
References 190
13 ADVANCES AND POSSIBLE APPLICATIONS OF HUMAN AMNION FOR THE MANAGEMENT OF LIVER DISEASE 197
Fabio Marongiu, Maria Paola Serra, Marcella Sini, Ezio Laconi, Marc C. Hansel, Kristen J. Skvorak, Roberto Gramignoli, and Stephen C. Strom
Introduction 197
Human Amnion for the Management of Liver Fibrosis 198
Amnion-Derived Hepatocytes and Their Possible Applications 199
Conclusions 204
References 205
14 AMNION-DERIVED CELLS FOR STROKE RESTORATIVE THERAPY 209
Naoki Tajiri, Loren E. Glover, and Cesar V. Borlongan
Introduction 209
Stem Cell Therapy: Beyond Stroke Neuroprotection 210
Therapeutic Potential of Adult Stem Cells 210
The Biology of Amnion-Derived Cells 211
Amnion-Derived Cells for Cell Therapy 212
Conclusion 215
References 216
15 PREGNANCY-ACQUIRED FETAL PROGENITORS AS NATURAL CELL THERAPY 221
Elke Seppanen, Nicholas M. Fisk,and Kiarash Khosrotehrani
Introduction 221
Fetal Cell Microchimerism, a Widespread Phenomenon 222
The Kinetics of Fetal Cell Detection 222
Factors Modifying the Level of Microchimerism 222
Detecting FMC 223
Homing and Plasticity of FMC 224
Hematopoietic Capacity of FMC 224
Epithelial, Neuronal and Hepatic Capacity of FMC 228
Mesenchymal Capacity of FMC 228
FMC Includes Functional Endothelial Progenitor Cells that Contribute to Tissue Repair 229
FMC Likely Includes Cells of Placental Origin 230
Conclusions 230
References 231
INDUSTRY REVIEW 235
16 PERINATAL STEM CELLS: AN INDUSTRY PERSPECTIVE 237
Kyle J. Cetrulo
Introduction 237
The Public Cord Blood Banking Industry 238
The Private Banking Industry 239
Research and Cord Blood Clinical Trials 240
The Mesenchymal Stem Cell Regenerative Medicine Industry 241
Whartons Jelly/Cord Tissue 242
Placental Stem Cells and Placental Tissue 243
Amniotic Fluid 244
Conclusion 245
References 245
17 PATENT PROTECTION OF STEM CELL INNOVATIONS 249
John R. Wetherell
The Role of Patents in Commercialization 249
Background of the Patent System 250
Patentable Subject Matter 251
Statutory Requirements for a Patent 252
Written Description/Enablement/Best Mode 254
Important Future Changes 256
18 INTERVIEW WITH FRANCES VERTER, FOUNDER OF PARENTS GUIDE TO CORD BLOOD FOUNDATION 259
Frances Verter and Kyle J. Cetrulo
References 269
19 UMBILICAL CORD BLOOD BANKING: AN OBSTETRICIANS PERSPECTIVE 271
Jordan H. Perlow
References 277
Index 279
