Perinatal Stem Cells

Kyle J. Cetrulo is the founder and CEO of Auxocell Laboraties, Inc, as well as the founder and Director of the Perinatal Stem Cell Society.?Co-editor of the first edition of Perinatal Stem Cells, Dr. Cetrulo is an active member of the stem cell research community, serving as Director of the International Cord Blood Society since 1998. Curtis Cetrulo Jr., M.D. is Assistant Professor of Surgery at Harvard Medical School, Boston. A co-editor of the first edition of Perinatal Stem Cells, he is also Director of the Reconstructive Transplantation Service in the Divisions of Transplant Surgery and Plastic and Reconstructive Surgery at Massachusetts General Hospital, and a senior investigator for the Composite Tissue Allograft Laboratory at Massachusetts General.

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 WHARTON’S 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

Wharton’s 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

Wharton’s 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 PARENT’S GUIDE TO CORD BLOOD FOUNDATION 259
Frances Verter and Kyle J. Cetrulo

References 269

19 UMBILICAL CORD BLOOD BANKING: AN OBSTETRICIAN’S PERSPECTIVE 271
Jordan H. Perlow

References 277

Index 279