Cell Therapy - Technologies, Markets and Companies

Table of Contents

Part I

0. Executive Summary. 21

1. Introduction to Cell Therapy. 25

• Introduction. 25
• Historical landmarks of cell therapy. 25
• Interrelationship of cell therapy technologies. 27
• Cells and organ transplantation. 27
• Cells and protein/gene therapy. 28
• Cell therapy and regenerative medicine. 29
• Cells therapy and tissue engineering. 29
• Therapy based on cells involved in disease. 30
• Advantages of therapeutic use of cells. 30
• Use of cells for improving drug delivery. 31

2. Cell Therapy Technologies. 33

• Introduction. 33
• Cell types used for therapy. 33
• Sources of cells. 33
• Xenografts. 34
• Cell lines. 34
• Immortalized cells. 34
• Blood component therapy. 34
• Therapeutic apheresis. 34
• Leukoreduction. 35
• Platelet therapy. 35
• Basic technologies for cell therapy. 36
• Cell culture. 36
• Observation of stem cell growth and viability. 36
• Companies involved in cell culture. 36
• Cell sorting. 38
• Flow cytometry. 38
• A dielectrophoretic system for cell separation. 39
• Molecular beacons for specific detection and isolation of stem cells. 39
• Multitarget magnetic activated cell sorter. 39
• Nanocytometry. 40
• Companies supplying cell sorters. 40
• Dynabead technology for cell sorting. 41
• ALDESORTER system for isolation of stem cells. 41
• Adult stem cell sorting by identification of surface markers. 42
• Cell analysis. 42
• Preservation of cells. 43
• Innovations in cryopreservation. 43
• Packaging of cells. 43
• Selective expansion of T cells for immunotherapy. 44
• Cloning and cell therapy. 44
• Techniques for cell manipulation. 45
• Cell-based drug discovery. 45
• Cells as vehicles for drug delivery. 48
• Drug delivery systems for cell therapy. 48
• Intravenous delivery of stem cells. 48
• Pharmacologically active microcarriers. 49
• Devices for delivery of cell therapy. 49
• Artificial cells. 50
• Applications of artificial cells. 50
• Cell encapsulation. 50
• Diffusion capsule for cells. 51
• Encapsulated cell biodelivery. 51
• Therapeutic applications of encapsulated cells. 52
• Nitric oxide delivery by encapsulated cells. 53
• Implantation of microencapulated genetically modified cells. 54
• Ferrofluid microcapsules for tracking with MRI. 54
• Companies involved in encapsulated cell technology. 54
• Electroporation. 55
• Gene therapy. 56
• Cell-mediated gene therapy. 56
• Fibroblasts. 56
• Chondrocyte. 57
• Skeletal muscle cells. 57
• Vascular smooth muscle cells. 58
• Keratinocytes. 58
• Hepatocytes. 58
• Lymphocytes. 59
• Mammalian artificial chromosomes. 59
• In vivo tracking of cells. 59
• Molecular imaging for tracking cells. 59
• MRI technologies for tracking cells. 60
• Superparamagnetic iron oxide nanoparticles as MRI contrast agents. 61
• Visualization of gene expression in vivo by MRI. 61
• Role of nanobiotechnology in development of cell therapy. 61
• Cell transplantation for development of organs. 62
• Cells transplantation and tolerance. 62
• Strategies to improve tolerance of transplanted cells. 63
• Encapsulation to prevent immune rejection. 63
• Prevention of rejection of xenotransplants. 63
• Expansion of allospecific regulatory T cells. 64
• Removal and replacement of pathogenic cells of the body. 64
• Therapeutic leukocytapheresis. 64

3. Stem Cells. 65

• Introduction. 65
• Biology of stem cells. 66
• Embryonic stem cells. 66
• Growth and differentiation of ESCs. 66
• Regulation of stem cell self-renewal and differentiation. 67
• Role of Pax3 in stem cell differentiation. 67
• ESCs and signaling pathways. 68
• Genetic signature of of stem cells. 68
• Epigenetics of hESCs. 68
• Chromatin as gene regulator for ESC development. 69
• Mechanism of differentiation of ESCs. 69
• Chemical regulation of stem cell differentiation. 70
• Comparison of development of human and mouse ESCs. 70
• In vitro differentiation of hESCs. 70
• Global transcription in pluripotent ESCs. 71
• Signaling pathways and transcription factors in ESCs. 71
• Stem cells in the pituitary gland. 71
• hESCs in stead of oocytes for reprogramming human somatic nuclei. 72
• Mechanism of regulation of stem cells for regeneration of body tissues. 72
• Role of microenvironments in the regulation of stem cells. 72
• Regulation and regeneration of intestinal stem cells. 73
• Parthenogenesis and human stem cells. 73
• Uniparental ESCs. 74
• Bone marrow stem cells. 74
• Hematopoietic stem cells. 74
• Role of HSCs in the immune system. 76
• Derivation of HSCs from ESCs. 76
• Mesenchymal stem cells. 77
• Multipotent adult progenitor cells. 78
• Side population (SP) stem cells. 79
• Differentiation of adult stem cells. 79
• Growth and differentiation of HSCs. 80
• Signaling pathways in the growth and differentiation of HSCs. 80
• Mathematical modeling of differentiation of HSCs. 80
• Role of prions in self renewal of HSCs. 81
• Sources of stem cells. 81
• Sources of of human embryonic stem cells. 81
• Nuclear transfer to obtain hESCs. 82
• Direct derivation of hESCs from embryos without nuclear transfer. 83
• Alternative methods of obtaining hESCs. 83
• Establishing hESC lines without destruction of embryo. 83
• Altered nuclear transfer. 84
• Small embryonic-like stem cells. 85
• Advantages and disadvantages of ESCs for transplantation. 85
• Use of ESC cultures as an alternative source of tissue for transplantation. 85
• Spermatogonial stem cells. 86
• Amniotic fluid as a source of stem cells. 87
• Placenta as source of stem cells. 87
• Amnion-derived multipotent progenitor cells. 87
• Placenta as a source of HSCs. 88
• Umbilical cord as a source of MSCs. 88
• Umbilical cord blood as source of neonatal stem cells. 88
• Cryopreservation of UCB stem cells. 89
• UCB as source of MSCs. 90
• Applications of UCB. 90
• Advantages of UCB. 90
• Limitations of the use of UCB. 91
• Licensing and patent disputes involving UCB. 92
• Infections following UCB transplants. 92
• Unanswered questions about UCB transplantation. 93
• Companies involved in UCB banking. 93
• UCB banking in the UK. 94
• US national UCB banking system. 95
• Future prospects of UCB as a source of stem cells. 96
• Induced pluripotent stem cells derived from human somatic cells. 96
• Characteristics of iPSCs. 97
• Use of retroviral vectors for generation of iPSCs. 97
• Use of non-integrating viral vectors for generation of iPSCs. 98
• iPSCs derived from blood. 98
• iPSCs derived from skin. 98
• Clinical relevance of iPSCs. 99
• Sources of adult human stem cells. 99
• Adipose tissue as a source of stem cells. 100
• Transforming adult adipose stem cells into other cells. 100
• iPSCs derived from adult human adipose stem cells. 100
• Skin as a source of stem cells. 101
• Follicle stem cells. 101
• Mesenchymal stem cells in skin. 101
• Epidermal neural crest stem cells. 102
• Regulation of stem cells in hair follicles. 102
• Controlling the maturation of embryonic skin stem cells. 102
• Stem cells in teeth. 103
• Peripheral blood stem cells. 103
• Spleen as a source of adult stem cells. 104
• Search for master stem cells. 104
• Adult stem cells vs embryonic stem cells. 105
• Transdifferentiation potential of adult stem cells. 105
• Neural crest stem cells from adult hair follicles. 106
• Stem cells obtained from blood in adults. 107
• VENT cells. 107
• Stem cell banking. 108
• Stem cell technologies. 108
• Analysis of stem cell growth and differentiation. 108
• Tracking self-renewal and expansion of transplanted muscle stem cells. 108
• Stem cell biomarkers. 109
• Endoglin as a functional biomarker of HSCs. 109
• STEMPRO&rec; EZChek™ for analysis of biomarkers of hESCs. 109
• SSEA-4 as biomarker of MSCs. 109
• p75NTR as a biomarker to isolate adipose tissue-derived stem cells. 110
• Neural stem cell biomarker. 110
• Protein expression profile as biomarker of stem cells. 110
• Real-time PCR for quantification of protein biomarkers. 111
• Study of stem cell genes. 111
• Gene inactivation to study hESCs. 111
• RNAi to study gene inactivation in hESCs. 111
• Study of ESC development by inducible RNAi. 112
• Targeting Induced Local Lesions in Genomes. 113
• Homologous recombination of ESCs. 113
• Immortalization of hESCs by telomerase. 113
• Gene modification in genomes of hESCs and hiPSCs using zinc-finger nuclease. 114
• miRNA and stem cells. 114
• Role of miRNAs in gene regulation during stem cell differentiation. 114
• Influence of miRNA on stem cell formation and maintenance. 115
• Transcriptional regulators of ESCs control miRNA gene expression. 115
• Stem cells and cloning. 116
• Cell nuclear replacement and cloning. 116
• Nuclear transfer and ESCs. 116
• Cloning from differentiated cells. 117
• Cloning mice from adult stem cells. 118
• Creating interspecies stem cells. 118
• Cloned cells for transplantation medicine. 119
• Claims of cloning of hESCs. 119
• Cytogenetics of embryonic stem cells. 120
• Engraftment, mobilization and expansion of stem cells. 121
• Adipogenesis induced by adipose tissue-derived stem cells. 122
• Antisense approach for preservation and expansion of stem cells. 122
• Enhancement of HSC engraftment by calcium-sensing receptor. 123
• Enhancement of stem cell differentiation by Homspera. 123
• Ex vivo expansion of human HSCs in culture. 123
• Ex vivo expansion of MSCs. 124
• Expansion of HSCs in culture by inhibiting aldehyde dehydrogenase. 124
• Expansion of adult stem cells by activation of Oct4. 125
• Expansion of transduced HSCs in vivo. 125
• Mobilization of HSCs by growth factors. 125
• Mobilization of stem cells by cytokines/chemokines. 126
• Mobilization of adult human HSCs by use of inhibitors. 127
• Mobilization of stem cells by HYC750. 127
• Mobilization of stem cells by hyperbaric oxygen. 127
• Mobilization by adenoviral vectors expressing angiogenic factors. 128
• Selective mobilization of progenitor cells from bone marrow. 128
• Selective Amplification. 129
• Stem cell mobilization by acetylcholine receptor agonists. 129
• Use of parathyroid hormone to increase HSC mobilzation. 129
• Expansion of stem cells in vivo by Notch receptor ligands. 129
• Technologies for inducing differentiation of stem cells. 130
• Use of lineage selection to induce differentiation of hESCs. 130
• Growth factor-induced differentiation of MAPCs. 130
• Neurotrophin-mediated survival and differentiation of hESCs. 130
• Generation of RBCs from hematopoietic stem cells. 131
• Generation of multiple types of WBCs from hESCs and iPSCs. 131
• Use of RNAi to expand the plasticity of autologous adult stem cells. 131
• Use of carbohydrate molecules to induce differentiation of stem cells. 132
• Mechanical strain to induce MSC differentiation. 132
• Limitations of the currently available stem cell lines in the US. 132
• Contaminating material in stem cell culture and measures to eliminate it. 133
• Stem cell separation. 134
• Stem cell culture. 135
• Conversion of stem cells to functioning adipocytes. 135
• Mass production of ESCs. 135
• Promoting survival of dissociated hESCs. 136
• Analysis and characterization of stem cells. 136
• Havesting and identification of EPCs. 136
• Labeling of stem cells. 137
• Quantum dots for labeling hMSCs. 137
• Imaging and tracking of stem cells in vivo. 138
• Quantum dot imaging for ESCs. 138
• Perfluorocarbon nanoparticles to track therapeutic cells in vivo. 138
• Project for imaging in stem cell therapy research. 138
• Applications of stem cells. 139
• Controlling the maintenance process of hematopoietic stem cells. 139
• Peripheral blood stem cell transplantation. 140
• Complications of PBSC transplantation in children. 140
• Stem cell transplantation for radiation sickness. 140
• Stem cells and human reproduction. 141
• Expansion of spermatogonial stem cells. 141
• Conversion of ESCs into spermatogonial stem cells. 141
• Conversion of stem cells to oocytes. 141
• ESCs for treatment of infertility in women. 142
• Cloning human embryos from oocytes matured in the laboratory. 142
• In utero stem cell transplantation. 143
• Innovations in delivery of stem cells. 143
• Immunological aspects of hESC transplantation. 144
• Immunosuppression to prevent rejection of hESC transplants. 144
• Histocompatibility of hESCs. 144
• Strategies for promoting immune tolerance of hESCs. 145
• Stem cells for organ vascularization. 146
• Activation of EphB4 to enhance angiogenesis by EPCs. 146
• Biofusion by genetically engineering stem cells. 147
• Stem cell gene therapy. 147
• Combination of gene therapy with nuclear transfer. 147
• Gene delivery to stem cells by artificial chromosome expression. 148
• Genetic manipulation of ESCs. 148
• Genetic engineering of human stem cells for enhancing angiogenesis. 148
• HSCs for gene therapy. 149
• Helper-dependent adenoviral vectors for gene transfer in ESCs. 149
• Lentiviral vectors for in vivo gene transfer to stem cells. 150
• Linker based sperm-mediated gene transfer technology. 150
• Mesenchymal stem cells for gene therapy. 150
• Molecular vibration for gene transfer. 150
• Regulation of gene expression for SC-based gene therapy. 151
• Stem cells and in utero gene therapy. 151
• Therapeutic applications for hematopoietic stem cell gene transfer. 151
• The future of hematopoietic stem cell gene therapy. 152
• Stem cell pharmaceutics. 152
• Stem cells for drug discovery. 152
• Advantages of using stem cells for drug discovery. 153
• Role of stem cells in therapeutic effects of drugs. 153
• Hepatocytes derived from hESCs. 153
• Cardiomyocytes derived from hESCs. 154
• ESCs as source of models for drug discovery. 155
• Engineered stem cells for drug delivery to the brain. 155
• Use of ESCs for toxicology and drug safety studies. 156
• European projects for safety testing of drugs using ESCs. 157
• Pharmaceutical manipulation of stem cells. 158
• Adverse effects of drugs on stem cells. 159
• Future challenges for stem cell technologies. 159
• Study of the molecular mechanism of cell differentiation. 160
• MBD3-deficient ESC line. 160
• In vivo study of human hemopoietic stem cells. 160
• Stem cell biology and cancer. 161
• Research into plasticity of stem cells from adults. 162
• Stem cells and aging. 162
• Activation of bone marrow stem cells into therapeutic cells. 163
• Role of nitric oxide in stem cell mobilization and differentiation. 163
• Stem cell genes. 164
• Gene expression in hESCs. 164
• The casanova gene in zebrafish. 164
• Nanog gene. 165
• Stem cell proteomics. 166
• hESC phosphoproteome. 166
• Proteomic studies of mesenchymal stem cells. 167
• Proteomic profiling of neural stem cells. 167
• Proteome Biology of Stem Cells Initiative. 167
• Genomic alterations in cultured hESCs. 168
• Hybrid embryos/cybrids for stem cell research. 168
• Generation of patient-specific pluripotent stem cells. 169
• Markers for characterizing hESC lines. 169
• Stem cell research at academic centers. 170
• International Regulome Consortium. 171
• Companies involved in stem cell technologies. 172
• Concluding remarks about stem cells. 176
• Challenges and future prospects of stem cell research. 176

4. Clinical Applications of Cell Therapy. 179

• Introduction. 179
• Cell therapy for hematological disorders. 179
• Transplantation of autologous hematopoietic stem cells. 179
• Hemophilias. 179
• Ex vivo cell/gene therapy of hemophilia B. 179
• Cell/gene therapy of hemophilia A. 180
• Hematopoietic stem cell therapy for thrombocytopenia. 181
• Stem cell transplant for sickle cell anemia. 181
• Treatment of chronic acquired anemias. 181
• Implantation of genetically engineered HSCs to deliver rhEpo. 182
• Drugs acting on stem cells for treatment of anemia. 182
• Stem cell therapy of hemoglobinopathies. 182
• Stem cells for treatment of immunoglobulin-light chain amyloidosis. 183
• Future prospects of cell therapy of hematological disorders. 183
• Cell therapy for immunological disorders. 184
• Role of dendritic cells in the immune system. 184
• Modifying immune responses of DCs by vaccination with lipiodol-siRNA mixtures. 184
• Stem cell therapy of chronic granulomatous disease. 185
• Stem cell therapy of X-linked severe combined immunodeficiency. 185
• Stem cell therapy of autoimmune disorders. 185
• Treatment of Crohn' s disease with stem cells. 186
• Treatment of rheumatoid arthritis with stem cells. 186
• Stem cell transplants for scleroderma. 186
• Role of T-Cells in immunological disorders. 187
• Autologous T-cells from adult stem cells. 188
• Cell therapy for graft vs host disease. 188
• Cell therapy for viral infections. 189
• T-cell therapy for CMV. 189
• T-cell therapy for HIV infection. 189
• T-cell immunity by Overlapping Peptide-pulsed Autologous Cells. 190
• Anti-HIV ribozyme delivered in hematopoietic progenitor cells. 190
• Dendritic-cell targeted DNA vaccine for HIV. 191
• Cell therapy of lysosomal storage diseases. 191
• Niemann-Pick disease. 191
• Gaucher' s disease. 192
• Fabry' s disease. 192
• Cell therapy for diabetes mellitus. 193
• Limitations of current treatment. 194
• Limitations of insulin therapy for diabetes mellitus. 194
• Limitations of pancreatic transplantation. 194
• Islet cell transplantation. 194
• Autologous pancreatic islet cell transplantation in chronic pancreatitis. 195
• Clinical trials of pancreatic islet cell transplants for diabetes. 195
• Drawbacks of islet cell therapy. 196
• Use of an antioxidant peptide to improve islet cell transplantation. 196
• Cdk-6 and cyclin D1 enhance human beta cell replication and function. 197
• A device for delivery of therapeutic cells in diabetes. 197
• Monitoring of islet cell transplants with MRI. 197
• Concluding remarks about allogeneic islet transplantation for diabetes. 197
• Encapsulation of insulin producing cells. 198
• Encapsulated porcine pancreatic islet cells for pancreas. 198
• Encapsulated insulinoma cells. 198
• Magnetocapsule enables imaging/tracking of islet cell transplants. 199
• Islet precursor cells. 199
• Dedifferentiation of β cells to promote regeneration. 200
• Xenotransplantation of embryonic pancreatic tissue. 200
• Non-pancreatic tissues for generation of insulin-producing cells. 201
• Exploiting maternal microchimerism to treat diabetes in the child. 201
• Bio-artificial substitutes for pancreas. 201
• Role of stem cells in the treatment of diabetes. 202
• Pancreatic stem cells. 202
• Embryonic stem cells for diabetes. 202
• Isolation of islet progenitor cells. 203
• Expansion of pancreatic progenitor cells in vitro. 204
• Human neural progenitor cells converted into insulin-producing cells. 204
• Insulin-producing cells derived from UCB stem cells. 204
• Stem cell injection into portal vein of diabetic patients. 205
• HSC transplantation to supplement immunosuppressant therapy. 205
• Dendritic cell-based therapy for type 1 diabetes. 205
• Gene therapy in diabetes. 206
• Viral vectors for gene therapy of diabetes. 206
• Genetically engineered dendritic cells. 207
• Genetically altered liver cells. 207
• Genetically modified stem cells. 207
• Companies developing cell therapy for diabetes. 208
• Concluding remarks about cell and gene therapy of diabetes. 208
• Cell therapy for liver disorders. 209
• Types of cells and methods of delivery for hepatic disorders. 210
• Bioartificial liver. 211
• Limitations of bioartificial liver. 211
• Stem cells for hepatic disorders. 211
• Deriving hepatocytes from commercially available hMSCs. 212
• Implantation of hepatic cells derived from hMSCs of adipose tissue. 213
• MSC derived molecules for reversing hepatic failure. 213
• Cell-based gene therapy for liver disorders. 213
• Transplantation of genetically modified fibroblasts. 214
• Transplantation of genetically modified hepatocytes. 214
• Intraperitoneal hepatocyte transplantation. 214
• Genetically modified hematopoietic stem cells. 214
• Clinical applications. 215
• Future prospects of cell-based therapy of hepatic disorders. 215
• Cell therapy of renal disorders. 216
• Bioartificial kidney. 216
• Bone marrow stem cells for renal disease. 216
• Human stem cells to prevent end stage renal disease. 217
• Role of stem cells in renal repair. 217
• Cell-based repair for vascular access failure in renal disease. 217
• Mesangial cell therapy. 218
• Cell therapy for pulmonary disorders. 218
• Delivery of cell therapy for pumonary disorders. 218
• Intratracheal injection of cells for pulmonary hypoplasia. 218
• Role of stem cells in pulmonary disorders. 218
• Lung tissue regeneration from stem cells. 219
• Role of stem cells in construction of the Cyberlung. 219
• Respiratory epithelial cells derived from UCB stem cells. 219
• Respiratory epithelial cells derived from hESCs. 220
• Lung tissue engineering with adipose stromal cells. 220
• Cell-based tissue-engineering of airway. 221
• Pulmonary disorders that are treatable by stem cells. 221
• Acute lung injury and ARDS treated with MSCs. 222
• Cystic fibrosis treatment with genetically engineered MSCs. 222
• Pulmonary arterial hypertension treatment with EPCs. 222
• Cell therapy for disorders of bones and joints. 223
• Repair of fractures and bone defects. 223
• Adult stem cells for bone grafting. 225
• Stem cells for repairing skull defects. 225
• Mesenchymal stem cells for repair of bones and joints. 225
• Osteocel. 228
• Cell therapy for osteonecrosis. 228
• Intrauterine use of MSCs for osteogenesis imperfecta. 228
• Stem cell-based bone tissue engineering. 229
• In vivo bone engineering as an alternative to cell transplantation. 230
• Osteoarthritis and other injuries to the joints. 230
• Mosaicplasty. 230
• Autologous cultured chondrocytes. 231
• Autologous intervertebral disc chondrocyte transplantation. 232
• Cartilage repair by genetically modified fibroblasts expressing TGF-&beta. 232
• Generation of cartilage from stem cells. 233
• Role of cell therapy in repair of knee cartilage injuries. 234
• Role of cells in the repair of anterior cruciate ligament injury. 236
• Autologous tenocyte implantation in rotator cuff injury repair. 236
• Platelet injection for tennis elbow. 236
• Cell therapy of rheumatoid arthritis. 237
• Cell therapy for regeneration. 237
• Stem cells for regeneration. 237
• Stem cells for regenerating organs. 238
• Umbilical cord blood for regeneration. 239
• Promotion of regeneration by Wnt/beta-catenin signaling. 239
• Role of stem cells in regeneration of esophageal epithelium. 240
• Cell therapy for regeneration of muscle wasting. 240
• MSCs for regeneration of ovaries following radiotherapy damage. 240
• Wound healing: skin and soft tissue repair. 241
• Cells to form skin substitutes for healing ulcers. 241
• CellSpray for wound repair. 242
• Role of follicular stem cells in skin and wound repair. 243
• Cell therapy for burns. 243
• Genetically engineered cells for wound repair. 244
• Cell therapy for corneal repair. 244
• Closure of incisions with laser guns and cells. 246
• Repair of aging skin by injecting autologous fibroblasts. 246
• Role of cells in tissue engineering and reconstructive surgery. 247
• Stem cells for tissue repair. 247
• Scaffolds for tissue engineering. 247
• Improving vascularization of engineered tissues. 248
• Enhancing vascularization by combining cell and gene therapy. 248
• Choosing cells for tissue engineering. 248
• ESCs vs adult SCs for tissue engineering. 248
• Use of adult MSCs for tissue engineering. 249
• Nanobiotechnology applied to cells for tissue engineering. 249
• Stem cells for tissue engineering of various organs. 250
• Engineering of healthy living teeth from stem cells. 250
• Adipose tissue-derived stem cells for breast reconstruction. 251
• Improving tissue engineering of bone by MSCs. 252
• Intra-uterine repair of congenital defects using amniotic fluid MSCs. 252
• Cell-based tissue engineering in genitourinary system. 253
• Urinary incontinence. 253
• Tissue engineering of urinary bladder. 254
• Label retaining urothelial cells for bladder repair. 254
• Repair of the pelvic floor with stem cells from the uterus. 255
• Reconstruction of vagina from stem cells. 255
• Facial skin regeneration by stem cells as an alternative to face transplant. 255
• Cell therapy for rejuvenation. 255
• Cell therapy for performance enhancement in sports. 256
• Application of stem cells in veterinary medicine. 256
• Use of stem cells to repair tendon injuries. 256
• Stem cells for spinal cord injury in dogs. 257

5. Cell Therapy for Cardiovascular Disorders. 259

• Introduction to cardiovascular disorders. 259
• Limitations of current therapies for myocardial ischemic disease. 259
• Tyes of cell therapy for cardiovascular disorders. 259
• Cell-mediated immune modulation for chronic heart disease. 260
• Role of splenic myocytes in repair of the injured heart. 261
• Human cardiovascular progenitor cells. 261
• Inducing the proliferation of cardiomyocytes. 262
• Small molecules to enhance myocardial repair by stem cells. 262
• Cell therapy for atherosclerotic coronary artery disease. 262
• MyoCell"! (Bioheart). 263
• Cardiac stem cells. 263
• Cardiomyocytes derived from epicardium. 264
• Methods of delivery of cells to the heart. 264
• Cellular cardiomyoplasty. 265
• IGF-1 delivery by nanofibers to improve cell therapy for MI. 265
• Non-invasive delivery of cells to the heart by MorphRguide catheter. 265
• Cell therapy for cardiac revascularization. 265
• Transplantation of cardiac progenitor cells for revascularization of myocardium. 265
• Stem cells to prevent restenosis after coronary angioplasty. 266
• Role of cells in cardiac tissue repair. 267
• Transplantation of myoblasts for myocardial infarction. 267
• Patching myocardial infarction with fibroblast culture. 268
• Cardiac repair with myoendothelial cells from skeletal muscle. 268
• Myocardial tissue engineering. 268
• Role of stem cells in repair of the heart. 269
• Role of stem cells in cardiac regeneration following injury. 269
• Cardiomyocytes derived from ESCs. 270
• Studies to identify subsets of progenitor cells suitable for cardiac repair. 271
• Technologies for preparation of stem cells for cardiovascular therapy. 272
• Pravastatin for expansion of endogenous progenitor and stem cells. 272
• Cytokine preconditioning of human fetal liver CD133+ SCs. 272
• Expansion of adult cardiac stem cells for transplantation. 273
• Role of ESCs in repair of the heart. 273
• ESC transplantation for tumor-free repair of the heart. 274
• Transplantation of stem cells for acute myocardial infarction. 274
• Autologous bone marrow-derived stem cell therapeutics. 274
• Autologous bone marrow-derived mesenchymal precursor stem cells. 275
• Transplantation of cord blood stem cells. 275
• Transplantation of hESCs. 275
• Transplantation of HSCs. 276
• Transplantation of autologous angiogenic cell precursors. 277
• Transplantation of adipose-derived stem cells. 277
• Intracoronary infusion of bone marrow-derived cells for AMI. 278
• Intracoronary infusion of mobilized peripheral blood stem cells. 278
• Transplantation of endothelial cells. 279
• Transplantation of cardiomyocytes differentiated from hESCs. 279
• Stem cell therapy for cardiac regeneration. 279
• Regeneration of the chronic myocardial infarcts by HSC therapy. 279
• Human mesenchymal stem cells for cardiac regeneration. 280
• In vivo tracking of MSCs transplanted in the heart. 281
• MSCs for hibernating myocardium. 281
• Simultaneous transplantation of MSCs and skeletal myoblasts. 282
• Transplantation of genetically modified cells. 282
• Transplantation of genetically modified MSCs. 282
• Transplantation of cells secreting vascular endothelial growth factor. 282
• Transplantation of genetically modified bone marrow stem cells. 283
• Cell transplantation for congestive heart failure. 283
• Myoblasts for treatment of congestive heart failure. 283
• Injection of adult stem cells for congestive heart failure. 284
• AngioCell gene therapy for congestive heart failure. 284
• Stem cell therapy for dilated cardiac myopathy. 285
• Role of cell therapy in cardiac arrhythmias. 285
• Atrioventricular conduction block. 286
• Genetically engineered cells as biological pacemakers. 286
• Ventricular tachycardia. 287
• Prevention of myoblast-induced arrhythmias by genetic engineering. 287
• ESCs for correction of congenital heart defects. 288
• Cardiac progenitors cells for treatment of heart disease. 288
• Autologus stem cells for chronic myocardial ischemia. 289
• Role of cells in cardiovascular tissue engineering. 289
• Construction of blood vessels with cells. 289
• Targeted delivery of endothelial progenitor cells labeled with nanoparticles. 290
• Fetal cardiomyocytes seeding in tissue-engineered cardiac grafts. 290
• UCB progenitor cells for engineering heart valves. 290
• Stem cell therapy for peripheral vascular disease. 291
• Clinical trials of cell therapy in cardiovascular disease. 292
• Mechanism of the benefit of cell therapy for heart disease. 294
• A critical evaluation of cell therapy for heart disease. 295
• Publications of clinical trials of cell therapy for CVD. 295
• Future directions for cell therapy of CVD. 296
• Prospects of adult stem cell therapy for repair of heart. 296
• Regeneration of cardiomyocytes without use of cardiac stem cells. 297

6. Cell Therapy for Cancer. 299

• Introduction. 299
• Cell therapy technologies for cancer. 299
• Cellular immunotherapy for cancer. 300
• Treatments for cancer by ex vivo mobilization of immune cells. 300
• Granulocytes as anticancer agents. 301
• Neutrophil granulocytes in antibody-based immunotherapy of cancer. 301
• Cancer vaccines. 302
• Autologous tumor cell vaccines. 302
• Vaccines that simultaneously target different cancer antigens. 303
• Gene modified cancer cells vaccines. 303
• GVAX cancer vaccines. 303
• Active immunotherapy based on antigen specific to the tumor. 304
• The use of dendritic cells for cancer vaccination. 304
• Basics of dendritic cell vaccines. 304
• Preclinical and clinical studies with DC vaccines. 304
• In vivo manipulation of dendritic cells. 305
• Autologous dendritic cells loaded ex vivo with telomerase mRNA. 305
• Dendritic/tumor cell fusion. 305
• Genetically modified dendritic cells. 306
• Limitations of DC vaccines for cancer. 307
• Future developments to enhance clinical efficacy of DC vaccines. 307
• Lymphocyte-based cancer therapies. 308
• Adoptive immunotherapy. 308
• Rescue of CD8+ T cells for use in tumor immunotherapy. 309
• Expansion of antigen-specific cytotoxic T lymphocytes. 310
• Genetically targeted T cells for treating B cell malignancies. 310
• Tumor infiltrating lymphocytes. 311
• Genetic engineering of tumor cells. 311
• Hybrid cell vaccination. 312
• Stem cell-based anticancer therapies. 312
• Stem cell transplantation in cancer. 312
• Peripheral blood stem cell transplantation. 312
• Autologous stem cell transplantation. 314
• Complications of stem cell transplants in cancer. 315
• Long-term results of HSC transplantation. 316
• Prediction of T-cell reconstitution after HSC transplantation. 316
• HSC transplantation followed by GM-CSF-secreting cell vaccines. 317
• Role of mesenchymal stem cells in cancer. 317
• Nonmyeloablative allogeneic hematopoietic stem cell transplantation. 318
• Umbilical cord blood transplant for leukemia. 318
• hESC-derived NK cells for treatment of cancer. 319
• ESC vaccine for prevention of lung cancer. 319
• Genetic modification of stem cells for cancer therapy. 320
• Genetic modification of hematopoietic stem cells. 320
• Use of hematopoietic stem cells to deliver suicide genes to tumors. 320
• Delivery of anticancer agents by genetically engineered MSCs. 320
• Mesenchymal progenitor cells for delivery of oncolytic adenoviruses. 321
• Genetically modified NSCs for treatment of neuroblastoma. 321
• Innovations in cell-based therapy of cancer. 322
• Use of immortalized cells. 322
• Cancer therapy based on natural killer cells. 322
• Mesothelin as a target for cancer immunotherapy. 322
• Nanomagnets for targeted cell-based cancer gene therapy. 323
• Implantation of genetically modified encapsulated cells for anticancer therapy. 323
• Antiangiogenesis therapy by implantation of microencapsulated cells. 323
• Recombinant tumor cells secreting fusion protein. 323
• NovaCaps® for pancreatic cancer. 324
• A device for filtering cancer and stem cells in the blood. 324
• Cancer stem cells. 324
• Role of integrative nuclear signaling in stem cell development. 325
• Cancer stem cell markers. 325
• Breast cancer stem cells. 325
• Role of intestinal stem cells in intestinal polyposis. 326
• Role of endothelial progenitor cells in tumor angiogenesis. 326
• Role of cancer stem cells in metastases. 327
• Therapeutic implications of cancer stem cells. 327
• Targeting cancer stem cells in leukemia. 328
• Targeting stem cells in ovarian cancer. 328
• Targeting cancer stem cells to screen anticancer drugs. 328
• Cell-based therapies for malignant brain tumors. 329
• Role of cancer stem cells in resistance to radiotherapy. 329
• Targeting stem cells in brain tumors. 329
• Neural stem cells for drug/gene delivery to brain tumors. 330
• Mesenchymal stem cells for the treatment of gliomas. 331
• Bone morphogenetic protein for inhibition of glioblastoma multiforme. 331
• Dendritic cell therapy for brain tumors. 331
• Encapsulated cells for brain tumors. 332
• Companies involved in cell-based cancer therapy. 333
• American Association for Cancer Research and ESCs. 334
• Future of cell-based immunotherapy for cancer. 335

7. Cell Therapy for Neurological Disorders. 337

• Introduction. 337
• Regeneration of the nervous system by endogenous stem cells. 337
• Molecular mechanism of neurogenesis. 337
• Generation of neurons from astroglia. 338
• In vivo cell replacement therapy by locally induced neural progenitor cells. 338
• Types of cells used for treatment of neurological disorders. 339
• Activated T lymphocytes. 339
• Differentiation of placenta-derived multipotent cells into neurons. 339
• Mesenchymal stem cells induced to secrete neurotrophic factors. 340
• Neural stem cells. 340
• Development of human CNS stem cells. 340
• Distinction between NSCs and intermediate neural progenitors. 341
• Embryonic stem cell-derived neurogenesis. 341
• Mechanism of migration of neural stem cells to sites of CNS injury. 343
• Monitoring of implanted NSCs labeled with nanoparticles. 343
• Neural progenitor cells. 343
• Neural stem cells as therapeutic delivery vehicles. 345
• Neural stem cells in the subventricular zone of the brain. 346
• Oligodendrocyte progenitor cells. 346
• Proteomics of neural stem cells. 346
• Regulation of neural stem cells in the brain. 347
• Study of neural differentiation of hESCs by NeuroStem Chip. 347
• Transformation of neural stem cells into other cell types. 347
• Use of epidermal neural crest stem cells for neurological disorders. 348
• Olfactory epithelium stem cells for transplantation in the CNS. 348
• Development of CNS cells from extraneural stem cells. 348
• Hair-follicle stem cells for neural repair. 349
• Stem cells from human umbilical cord blood for CNS disorders. 349
• Immortalized cells for CNS disorders. 350
• Fetal tissue transplants. 350
• Choroid plexus cells. 351
• Laboratory mice with human brain cells. 351
• Expansion of adult human neural progenitors. 352
• Neurospheres. 352
• Dental pulp cells for neuroprotection. 352
• Ideal cells for transplantation into the nervous system. 353
• Cell therapy techniques for neurological applications. 353
• Stem cells preparations for CNS disorders. 353
• Neuronal differentiation of stem cells. 354
• hESCs for CNS repair. 355
• Enhancement of growth of stem cells in the brain by drugs. 355
• Carbon nanotubes to aid stem cell therapy of neurological disorders. 356
• Use of neural stem cells to construct the blood brain barrier. 356
• Tracking of stem cells in the CNS by nanoparticles and MRI. 357
• Methods of delivery of cells to the CNS. 357
• Encapsulated cells. 358
• CNS neotissue implant. 358
• Intrathecal delivery of stem cells. 358
• CNS delivery of cells by catheters. 359
• Intravascular administration. 359
• Cells used for gene therapy of neurological disorders. 360
• Fibroblasts. 360
• Stem cells. 361
• Neuronal cells. 361
• Immortalized neural progenitor cells. 361
• Astrocytes. 362
• Cerebral endothelial cells. 362
• Human retinal pigmented epithelial cells. 363
• Neurological disorders amenable to cell therapy. 363
• Neuroprotection by cell therapy. 363
• Cells secreting neuroprotective substances. 363
• Stem cells for neuroprotection. 364
• Neuroprotection by intravenous administration of HSCs. 364
• Human UCB-derived stem cells for the aging brain. 364
• Neurodegenerative disorders. 364
• Role of stem cells in neurodegenerative disorders. 365
• MSCs for therapy of neurodegenerative disorders. 365
• Role of NSCs in disorders associated with aging brain. 366
• NSCs for improving memory. 367
• Parkinson' s disease. 367
• Origin and fate of dopamine neurons. 369
• Human dopaminergic neurons for PD. 369
• Graft survival-enhancing drugs. 369
• Xenografting porcine fetal neurons. 370
• Encapsulated cells for PD. 370
• Stem cells for PD. 371
• Stem cells for production of glial derived neurotrophic factor. 373
• Potential of regeneration of endogenous stem cells in PD. 373
• Human retinal pigment epithelium cells for PD. 374
• Coaxing hESCs to produce dopamine. 374
• Tumorigenic potential of transplantated dopaminergic hESCs. 374
• Delivery of cells for PD. 375
• MSCs for multiple system atrophy. 375
• Cell therapy for Huntington' s disease. 375
• Fetal striatal cell transplantation. 375
• Transplantation of encapsulated porcine choroids plexus cells. 376
• Cell therapy for Alzheimer' s disease. 376
• Neural stem cell implantation for Alzheimer' s disease. 377
• Implantation of genetically engineered cells producing NGF. 377
• Cell therapy for amyotrophic lateral sclerosis. 378
• Cell nuclear replacement technique for study of ALS. 378
• Use of stem cells for ALS. 378
• Transplantation of glial restricted precursors in ALS. 380
• Stem cell-based drug discovery for ALS. 380
• Cell therapy for lysosomal storage disorders. 380
• Cell therapy for Batten disease. 380
• Genetically modified HSCs for metachromatic leukodystrophy. 381
• Cell therapy for demyelinating disorders. 382
• Hematopoietic stem cell transplantation for multiple sclerosis. 382
• Embryonic stem cells for remyelination. 383
• Neural precursor cells for neuroprotection in multiple sclerosis. 383
• Stem cells for chronic inflammatory demyelinating polyneuropathy. 384
• Fusokine method of personalized cell therapy of multiple sclerosis. 384
• Cell therapy of stroke. 384
• Transplantation of encapsulated porcine choroids plexus. 385
• Transplantation of fetal porcine cells. 385
• Adult stem cell therapy in stroke. 385
• Implantation of genetically programmed ESCs. 386
• Intravenous infusion of marrow stromal cells. 386
• Intravenous infusion of UCB stem cells. 387
• Intracerebral administration of human adipose tissue stromal cells. 387
• Intracerebral administration of multipotent adult progenitor cells. 388
• Neural stem cell therapy for stroke. 388
• Future of cell therapy for stroke. 389
• Cell therapy of traumatic brain injury. 390
• Cell/gene therapy for TBI. 390
• Clinical trials of autologous HSC therapy for TBI. 391
• Limitations of stem cell therapy for acute TBI. 391
• Improving the microenvironments of transplanted cells in TBI. 391
• Cell therapy for spinal cord injury. 392
• Fetal neural grafts for SCI. 392
• Olfactory-ensheathing cells for SCI. 392
• Oligodendrocyte precursor cells for treatment of SCI. 393
• Schwann cell transplants for SCI. 393
• Transplantation of glial cells for SCI. 393
• Stem cells for SCI. 394
• Bone marrow stem cells for SCI. 394
• Embryonic stem cells for SCI. 394
• Transplantation of MSCs for SCI. 395
• Transplantation of NSCs for SCI. 395
• Transdifferentiation of BM stem cells into cholinergic neurons for SCI. 396
• Spinal stem cells for treatment of ischemic injury of spinal cord. 396
• Combined approaches for regeneration in SCI. 397
• Combined cell/gene therapy for SCI. 397
• Delivery of cells in SCI. 397
• Intrathecal injection of cells labeled with magnetic nanoparticles. 398
• Intravenous injection of stem cells for spinal cord repair. 398
• Clinical applications of stem cells for SCI. 398
• Autologous bone marrow cell transplantation for SCI. 398
• Cell therapy of syringomyelia. 399
• Umbilical cord blood stem cells for neurogenetic disorders. 399
• UCB stem cells for Krabbe' s disease. 399
• UCB stem cells for Hurler' s syndrome. 399
• UCB stem cells for Sanfilippo syndrome type B. 400
• Combination of cell and gene therapy for Krabbe' s disease. 400
• Cell therapy of epilepsy. 401
• Cell therapy of posttraumatic epilepsy. 401
• Cell therapy for temporal lobe epilepsy. 401
• Cell therapy for pharmacoresistant epilepsies. 402
• Cell therapy for developmental neurological disorders. 402
• Cell therapy for cerebral palsy. 402
• Cell therapy for muscular dystrophy. 403
• Cell transplant for Duchenne muscular dystrophy. 403
• Myoblast-based gene transfer. 404
• Transplantation of myoblasts lacking the MyoD gene. 404
• HSCs for DMD. 405
• Improvement of DMD therapy by using muscle-derived stem cells. 405
• Combination of cell and pharmacotherapy for DMD. 406
• Myoblast injection for treatment of other muscular dystrophies. 406
• Cell therapy for Autism. 407
• Management of chronic intractable pain by cell therapy. 407
• Implantation of chromaffin cells. 407
• Role of stem cells in management of pain. 408
• Implantation of astrocytes secreting enkephalin. 408
• Cells for delivery of antinociceptive molecules. 409
• Implantation of genetically engineered cells. 409
• Cell therapy for low back pain. 409
• Cell therapy for retinal degenerative disorders. 410
• Genetically engineered retinal pigmented epithelial cell lines. 411
• Delivery of CNTF by encapsulated cell intraocular implants. 411
• Stem cell transplantation in the retina. 411
• Isolation of RPE cells from hESCs using transcriptomics. 412
• ESCs for retinal degenerative disorders. 412
• Neuroprotective effect of neural progenitor cell transplantation. 412
• Human retinal stem cells. 413
• Combining cell and gene therapies for retinal disorders. 413
• Stem cell therapy for hearing loss. 413
• Cell thery for peripheral nerve lesions. 414
• Cell transplants for peripheral nerve injuries. 414
• Treatment of diabetic neuropathy with endothelial progenitor cells. 414
• Clinical trials of cell therapy in neurological disorders. 415
• Future prospects for cell therapy of CNS disorders. 416

8. Ethical, Regulatory, and Safety Aspects of Cell Therapy. 417

• Introduction. 417
• Safety issues of cell therapy. 417
• Immune-mediated reactions to transpanted stem cells. 417
• Human virus infections associated with stem cell transplantation. 418
• Herpes simplex virus type 1. 418
• Cytomegalovirus. 418
• Opportunistic infections among hematopoietic stem cell transplant recipients. 418
• Carcinogenic potential of stem cells and its prevention. 419
• FDA safety regulations for cell and tissue products. 419
• FDA Guidance on license applications for umbilical cord blood products. 420
• Political and ethical aspects of hESC research in the US. 420
• Ethical issues concerning fetal tissues. 420
• Morality and hESC research. 421
• Opponents of hESC research in the US. 421
• Ban on cloning and impact on hESC research. 421
• Political aspects of human hESC research in the US. 422
• Use of hESCs in NIH-supported research. 422
• Public opinion in the US about hESC research. 424
• Scientists' view of stem cell research in the US. 425
• New developments in stem cell research in the US. 427
• Human stem cell cloning in the US. 428
• Stem cell guidelines of various US institutions. 428
• Ethics of transplanting human NSCs into the brains of nonhuman primates. 429
• Stem cell lines available worldwide. 430
• Stem cell policies around the world. 431
• Countries with no defined policies on hESC research. 431
• Australia. 432
• Canada. 432
• China. 433
• Denmark. 433
• France. 434
• Germany. 434
• India. 436
• Ireland. 436
• Israel. 437
• Italy. 437
• Japan. 438
• The Netherlands. 438
• Saudi Arabia. 439
• Singapore. 439
• South Africa. 439
• South Korea. 440
• Spain. 440
• Sweden. 440
• Switzerland. 441
• United Kingdom. 441
• ESC bank. 442
• European Union. 443
• EU guidelines for stem cell research. 443
• EMBO' s recommendations for stem cell research. 444
• United Nations, cloning and nuclear transfer. 445
• The Embryo Project for information on ESC research. 446
• Concluding remarks about ethics of ESC research. 446
• Ethical issues concerning umbilical cord blood. 446
• Cell therapy tourism. 447
• Regulatory issues. 447
• Regulation of cord blood banks in the US. 447
• Regulatory issues for biotechnology-derived drugs. 448
• Regulation of cell selection devices for production of PBSCs at point of care. 448
• FDA rules for human cells and tissues. 449
• FDA regulation of fetal cellular or tissue products. 449
• FDA and clinical trials using hESCs. 450
• Cell and gene therapy INDs placed on hold by the FDA. 451
• NIH regulation of fetal cellular or tissue products. 451
• Regulatory issues for genetically engineered cell transplants. 452
• FDA guidelines for human tissue transplantation. 452
• Xenotransplantation. 452
• Clinical Protocol Review and Oversight. 452
• Informed consent and patient education. 453
• Xenotransplantation product sources. 453
• FDA guidelines for xenografts. 454
• Regulations relevant to cell therapy in the European Union. 455
• Regulations about use of stem cells. 456
• EMEA regulation of cell/gene therapy. 456
• Guidelines for cell therapy in the UK. 457
• Clinical trials in cell therapy. 457
• Stem cell patents. 458
• Stem cell patents in the United States. 458
• Current status of Thomson patents at WARF. 459
• Stem cell patents in the European Union. 459

9. References. 461

Tables

• Table 1 1: Landmarks in the history of cell therapy. 25
• Table 1 2: Examples of cells involved in various diseases. 30
• Table 2 1: Types of human cells used in cell therapy. 33
• Table 2 2: A selection of companies providing cell culture media. 37
• Table 2 3: A sampling of companies supplying cell sorters. 40
• Table 2 4: Companies involved in cell-based drug discovery. 46
• Table 2 5: Methods of delivery of cells for therapeutic purposes. 48
• Table 2 6: Therapeutic applications of encapsulated cells. 52
• Table 2 7: Companies working on encapsulated cell technology. 54
• Table 2 8: Molecular imaging methods for tracking cells in vivo. 60
• Table 3 1: Companies involved in cord blood banking as a source of stem cells. 93
• Table 3 2: Sources of adult human stem cells. 99
• Table 3 3: Enhancing engraftment, mobilization and expansion of stem cells. 121
• Table 3 4: Applications of stem cells. 139
• Table 3 5: Growth factors with positive effects on stem cells and applications. 158
• Table 3 6: Examples of drugs that induce granulocytopenia at stem cell level. 159
• Table 3 7: Academic institutes involved in stem cell research. 170
• Table 3 8: Companies involved in stem cell technologies. 172
• Table 4 1: Therapeutic applications of regulatory T cells (T-regs). 187
• Table 4 2: Various tissue/cell therapy approaches to the treatment of type 1 diabetes. 193
• Table 4 3: Companies involved in cell therapy for insulin-dependent diabetes. 208
• Table 4 4: Major pulmonary disorders potentially treatable by stem cell manipulation. 221
• Table 4 5: Cell-based repair of knee cartilage damage. 235
• Table 5 1: Classification of various types of cell therapy for cardiovascular disorders. 259
• Table 5 2: Clinical trials of cell therapy in cardiovascular disease. 292
• Table 6 1: Cell therapy technologies used for cancer. 299
• Table 6 2: Companies involved in developing cell-based therapies for cancer. 333
• Table 7 1: Experimental use of immortalized cells for CNS disorders. 350
• Table 7 2: Methods for delivering cell therapies in CNS disorders. 357
• Table 7 3: Neurological disorders amenable to cell therapy. 363
• Table 7 4: Types of cell used for investigative treatment of Parkinson' s disease. 368
• Table 7 5: Status of cell therapies for Parkinson' s disease. 368
• Table 7 6: Clinical trials with cell-based therapies in neurological disorders. 415
• Table 8 1: Possible adverse reactions and safety issues of cell therapy. 417
• Table 8 2: Listed numbers of stem cell lines around the world as of end of 2008. 430
• Table 8 3: Stem cell policies around the world. 431

Figures

• Figure 1 1: Interrelationships of cell therapy to other technologies. 27
• Figure 1 2: Interrelationships of gene, cell and protein therapies. 29
• Figure 3 1: A simplified biological scheme of embryonic stem Cells. 66
• Figure 3 2: Steps of iPS cell production. 97
• Figure 3 3: Flow chart of development of stem cells with potential bottlenecks. 176
• Figure 5 1: hESC-derived cardiomyocytes from laboratory to bedside. 271
• Figure 6 1: A scheme of generation and administration of tumor antigen-pulsed dendritic cells. 307
• Figure 6 2: Stem cell transplantation techniques. 313
• Figure 7 1: Stem cells that can give rise to neurons. 345
• Figure 7 2: Approaches to stem cell therapy in stroke. 386

Part II

10. Markets and Future Prospects for Cell Therapy. 9

• Introduction. 9
• Methods for estimation of cell therapy markets. 9
• Potential markets for cell therapy. 10
• Markets according to technologies. 10
• Stem cell transplant. 10
• hESC markets. 10
• Blood transfusion market. 10
• Cord blood collection and storage. 11
• Cell therapy and related technologies. 11
• Cell therapy markets according to therapeutic area. 11
• Bone and joint disorders. 12
• Cancer. 12
• Cardiovascular disorders. 12
• Diabetes mellitus. 13
• Liver disorders. 13
• Neurological disorders. 14
• Retinal degenerative diseases market. 14
• Skin and wound care. 15
• Urinary incontinence. 15
• Reconstruction of teeth by stem cell implants. 15
• Market size according to geographical areas. 15
• Unmet market needs in cell therapy. 16
• Drivers of growth of cell therapy markets. 17
• Role of stem cells in regenerative medicine. 17
• Role of cells in markets for artificial organs. 18
• Increase of R&D expense on cell therapy. 18
• Increased used of cell-based drug discovery. 18
• Impact of emerging healthcare trends on cell therapy markets. 18
• Future prospects of cell therapy. 18
• Embryonic stem cell research around the world. 19
• Consortia for ESC research in Europe. 19
• EuroStemCell. 19
• FunGenES. 20
• ESTOOLS. 21
• UK National Stem Cell Network. 22
• Ethical concerns about commercialization of embryonic stem cells. 22
• Education of the physicians. 22
• Public education. 22
• NIH support of stem cell research. 23
• Funding of stem cell research from non-federal sources. 23
• Prospects of venture capital support for stem cell companies. 25
• Cell therapy in the developing countries. 25
• Guidelines for stem cell therapies. 26
• Business strategies. 27
• Formation of networks. 27
• Future market potential of adult vs embryonic stem cells. 28

11. Companies Involved in Cell Therapy. 29

• Introduction. 29
• Profiles of selected companies. 31
• Collaborations. 324

12. Academic Institutions. 333

• Introduction. 333
• Stem cell center. 333
• Profiles of institutions. 334
• Collaborations. 416

Tables

• Table 10 1: Market size according to cell therapy and related technologies 2008-2018. 10
• Table 10 2: Market size according to therapeutic areas for cell therapy 2008-2018. 11
• Table 10 3: Cell therapy markets for cardiovascular disorders 2008-2018. 13
• Table 10 4: Values of cell therapies for neurological disorders 2008-2018. 14
• Table 10 5: Total cell therapy market according to geographical areas 2008-2018. 16
• Table 10 6: Cord blood market according to geographical areas 2008-2018. 16
• Table 10 7: Stem cells transplant market according to geographical areas 2008-2018. 16
• Table 11 1: Publicly traded cell therapy companies. 29
• Table 11 2: Selected collaborations of cell therapy companies. 324
• Table 12 1: Therapeutic uses of stem cells. 341
• Table 12 2: Commercial collaborations of academic institutes in the US relevant to stem cells. 416

Figures

• Figure 10 1: Unmet needs in cell therapy. 17