Abstract
Summary
This report describes and evaluates cell therapy technologies and methods,
which have already started to play an important role in the practice of
medicine. Hematopoietic stem cell transplantation is replacing the old
fashioned bone marrow transplants. Role of cells in drug discovery is also
described. Cell therapy is bound to become a part of medical practice.
Stem cells are discussed in detail in one chapter. Some light is thrown on the
current controversy of embryonic sources of stem cells and comparison with
adult sources. Other sources of stem cells such as the placenta, cord blood
and fat removed by liposuction are also discussed. Stem cells can also be
genetically modified prior to transplantation.
Cell therapy technologies overlap with those of gene therapy, cancer vaccines,
drug delivery, tissue engineering and regenerative medicine. Pharmaceutical
applications of stem cells including those in drug discovery are also
described. Various types of cells used, methods of preparation and culture,
encapsulation and genetic engineering of cells are discussed. Sources of
cells, both human and animal (xenotransplantation) are discussed. Methods of
delivery of cell therapy range from injections to surgical implantation using
special devices.
Cell therapy has applications in a large number of disorders. The most
important are diseases of the nervous system and cancer which are the topics
for separate chapters. Other applications include cardiac disorders
(myocardial infarction and heart failure), diabetes mellitus, diseases of
bones and joints, genetic disorders, and wounds of the skin and soft tissues.
Regulatory and ethical issues involving cell therapy are important and are
discussed. Current political debate on the use of stem cells from embryonic
sources (hESCs) is also presented. Safety is an essential consideration of any
new therapy and regulations for cell therapy are those for biological
preparations.
The cell-based markets was analyzed for 2011, and projected to 2021.The
markets are analyzed according to therapeutic categories, technologies and
geographical areas. The largest expansion will be in diseases of the central
nervous system, cancer and cardiovascular disorders. Skin and soft tissue
repair as well as diabetes mellitus will be other major markets.
The number of companies involved in cell therapy has increased remarkably
during the past few years. More than 500 companies have been identified to be
involved in cell therapy and 280 of these are profiled in part II of the
report along with tabulation of 270 alliances. Of these companies, 154 are
involved in stem cells. Profiles of 69 academic institutions in the US
involved in cell therapy are also included in part II along with their
commercial collaborations. The text is supplemented with 52 Tables and 11
Figures. The bibliography contains 1,050 selected references, which are cited
in the text.
Table of Contents
Part I
0. Executive Summary 24
1. Introduction to Cell Therapy 28
- Introduction 28
- Historical landmarks of cell therapy 28
- Interrelationship of cell therapy technologies 30
- Cells and organ transplantation 30
- Cells and protein/gene therapy 31
- Cell therapy and regenerative medicine 32
- Cells therapy and tissue engineering 32
- Therapy based on cells involved in disease 33
- Advantages of therapeutic use of cells 33
- Cell-based drug delivery 34
- Cells as vehicles for gene delivery 34
- Red blood cells as vehicles for drug delivery 34
- Advantages of cell-based drug delivery 35
- Limitations of cell-based drug delivery 35
2. Cell Therapy Technologies 36
- Introduction 36
- Cell types used for therapy 36
- Sources of cells 36
- Xenografts 37
- Cell lines 37
- Immortalized cells 37
- Blood component therapy 37
- Therapeutic apheresis 37
- Leukoreduction 38
- Platelet therapy 38
- Basic technologies for cell therapy 39
- Cell culture 39
- Automated cell culture devices 39
- Cell culture for adoptive cell therapy 40
- Observation of stem cell growth and viability 40
- Companies involved in cell culture 40
- Cell sorting 42
- Flow cytometry 42
- A dielectrophoretic system for cell separation 43
- Adult stem cell sorting by identification of surface markers 43
- ALDESORTER system for isolation of stem cells 43
- Dynabead technology for cell sorting 43
- Molecular beacons for specific detection and isolation of stem cells 44
- Multitarget magnetic activated cell sorter 44
- Nanocytometry 44
- Scepter™ cytometer 45
- Companies supplying cell sorters 45
- Cell analysis 46
- Cell analyzers 46
- In vivo cell imaging 46
- Measuring cell density 47
- Single-cell gene expression analysis 47
- Preservation of cells 48
- Innovations in cryopreservation 48
- Packaging of cells 49
- Selective expansion of T cells for immunotherapy 49
- Cloning and cell therapy 50
- Techniques for cell manipulation 50
- Cell-based drug discovery 51
- Advantages and limitations of cell-based assays for drug discovery 51
- Advantages and limitations of cell-based toxicity screening 51
- Quality control of cells for drug discovery 52
- Companies involved in cell-based drug discovery 52
- Drug delivery systems for cell therapy 54
- Intravenous delivery of stem cells 54
- Intraarterial delivery of stem cells 54
- Pharmacologically active microcarriers 54
- Devices for delivery of cell therapy 55
- Artificial cells 56
- Applications of artificial cells 56
- Cell encapsulation 56
- Diffusion capsule for cells 57
- Encapsulated cell biodelivery 57
- Therapeutic applications of encapsulated cells 58
- Nitric oxide delivery by encapsulated cells 59
- Implantation of microencapulated genetically modified cells 59
- Ferrofluid microcapsules for tracking with MRI 60
- Companies involved in encapsulated cell technology 60
- Electroporation 61
- Gene therapy 61
- Cell-mediated gene therapy 62
- Fibroblasts 62
- Chondrocyte 63
- Skeletal muscle cells 63
- Vascular smooth muscle cells 64
- Keratinocytes 64
- Hepatocytes 64
- Lymphocytes 65
- Mammalian artificial chromosomes 65
- In vivo tracking of cells 65
- Molecular imaging for tracking cells 65
- MRI technologies for tracking cells 66
- Superparamagnetic iron oxide nanoparticles as MRI contrast agents 67
- Visualization of gene expression in vivo by MRI 67
- Role of nanobiotechnology in development of cell therapy 68
- Cell transplantation for development of organs 68
- Cells transplantation and tolerance 69
- Strategies to improve tolerance of transplanted cells 69
- Encapsulation to prevent immune rejection 69
- Prevention of rejection of xenotransplants 69
- Expansion of allospecific regulatory T cells 70
- Removal and replacement of pathogenic cells of the body 70
- Therapeutic leukocytapheresis 70
3. Stem Cells 72
- Introduction 72
- Biology of stem cells 73
- Embryonic stem cells 73
- Growth and differentiation of ESCs 73
- Mechanisms of differentiation of ESCs 74
- Chemical regulation of stem cell differentiation 74
- In vitro differentiation of hESCs 74
- SIRT1 regulation during stem cell differentiation 74
- Regulation of stem cell self-renewal and differentiation 75
- hESCs for reprogramming human somatic nuclei 75
- Stem cells differentiation in the pituitary gland 75
- Influence of microenvironment on ESCs 76
- Role of genes in differentiation of ESCs 76
- Global transcription in pluripotent ESCs 76
- Role of p53 tumor suppressor gene in stem cell differentiation 77
- Role of Pax3 gene in stem cell differentiation 77
- Signaling pathways and ESC genes 77
- Epigenetics of hESCs 78
- Chromatin as gene regulator for ESC development 78
- Comparison of development of human and mouse ESCs 79
- Mechanism of regulation of stem cells for regeneration of body tissues
79
- Role of microenvironments in the regulation of stem cells 80
- Regulation and regeneration of intestinal stem cells 80
- Parthenogenesis and human stem cells 80
- Uniparental ESCs 81
- Bone marrow stem cells 82
- Hematopoietic stem cells 82
- Role of HSCs in the immune system 84
- Derivation of HSCs from ESCs 84
- Mesenchymal stem cells 84
- Multipotent adult progenitor cells 86
- Side population (SP) stem cells 86
- Differentiation of adult stem cells 87
- Growth and differentiation of HSCs 88
- Signaling pathways in the growth and differentiation of HSCs 88
- Mathematical modeling of differentiation of HSCs 88
- Role of prions in self renewal of HSCs 89
- Sources of stem cells 89
- Sources of of human embryonic stem cells 89
- Nuclear transfer to obtain hESCs 89
- Direct derivation of hESCs from embryos without nuclear transfer 90
- Alternative methods of obtaining hESCs 91
- Establishing hESC lines without destruction of embryo 91
- Altered nuclear transfer 92
- Small embryonic-like stem cells 92
- Advantages and disadvantages of ESCs for transplantation 93
- Use of ESC cultures as an alternative source of tissue for transplantation
93
- Spermatogonial stem cells 94
- Amniotic fluid as a source of stem cells 95
- Amniotic fluid stem cells for tissue repair and regeneration 95
- Generation of iPS cells from AF cells 95
- Placenta as source of stem cells 96
- Amnion-derived multipotent progenitor cells 96
- Placenta as a source of HSCs 97
- Umbilical cord as a source of MSCs 97
- Umbilical cord blood as source of neonatal stem cells 97
- Cryopreservation of UCB stem cells 98
- UCB as source of MSCs 99
- Applications of UCB 99
- Advantages of UCB 99
- Limitations of the use of UCB 100
- Licensing and patent disputes involving UCB 101
- Infections following UCB transplants 101
- Unanswered questions about UCB transplantation 102
- Companies involved in UCB banking 102
- UCB banking in the UK 103
- US national UCB banking system 104
- Future prospects of UCB as a source of stem cells 105
- Induced pluripotent stem cells derived from human somatic cells 105
- Characteristics of iPSCs 106
- DNA methylation patterns of iPS cells 106
- iPSCs derived from oocytes through SCNT 107
- iPSCs derived from skin 107
- iPSCs derived from blood 107
- Use of retroviral vectors for generation of iPSCs 108
- Use of non-integrating viral vectors for generation of iPSCs 109
- Generation of clinically relevant iPSCs 109
- Generation of RBCs from iPSCs 110
- iPSCs and disease modeling 110
- iPSCs for patient-specific regenerative medicine 111
- Concluding remarks about clinical potential of iPSCs 111
- Induced conditional self-renewing progenitor cells 112
- Sources of adult human stem cells 112
- Adipose tissue as a source of stem cells 112
- Intravenous infusion of adipose tissue derived MSCs 113
- iPSCs derived from adult human adipose stem cells 113
- Regulation of adipose stem cells differentiation 113
- Transforming adult adipose stem cells into other cells 114
- Multipotent stem-like cells derived from vascular endothelial cells 114
- Skin as a source of stem cells 114
- Controlling the maturation of embryonic skin stem cells 114
- Epidermal neural crest stem cells 115
- Follicle stem cells 115
- Mesenchymal stem cells in skin 116
- Regulation of stem cells in hair follicles 116
- Skin-derived precursor cells 116
- Stem cells in teeth 117
- Peripheral blood stem cells 117
- Spleen as a source of adult stem cells 118
- Search for master stem cells 118
- Vascular cell platform to self-renew adult HSC 119
- Adult stem cells vs embryonic stem cells 119
- Biological differences between adult and embryonic stem cells 119
- Neural crest stem cells from adult hair follicles 120
- Transdifferentiation potential of adult stem cells 120
- Limitations of adult stem cells 121
- Comparison of human stem cells according to derivation 122
- VENT cells 122
- Stem cell banking 122
- Stem cell technologies 123
- Analysis of stem cell growth and differentiation 123
- Tracking self-renewal and expansion of transplanted muscle stem cells
123
- Stem cell biomarkers 123
- Endoglin as a functional biomarker of HSCs 124
- STEMPRO&rec; EZChek™ for analysis of biomarkers of hESCs 124
- SSEA-4 as biomarker of MSCs 124
- p75NTR as a biomarker to isolate adipose tissue-derived stem cells 124
- Neural stem cell biomarker 125
- Protein expression profile as biomarker of stem cells 125
- Real-time PCR for quantification of protein biomarkers 125
- Study of stem cell pathways 126
- Study of stem cell genes 126
- Gene inactivation to study hESCs 127
- RNAi to study gene inactivation in hESCs 127
- Study of ESC development by inducible RNAi 127
- Targeting Induced Local Lesions in Genomes 128
- Homologous recombination of ESCs 128
- Immortalization of hESCs by telomerase 128
- Gene modification in genomes of hESCs and hiPSCs using zinc-finger
nuclease 129
- miRNA and stem cells 129
- Role of miRNAs in gene regulation during stem cell differentiation 129
- Influence of miRNA on stem cell formation and maintenance 130
- Transcriptional regulators of ESCs control miRNA gene expression 131
- Stem cells and cloning 131
- Cell nuclear replacement and cloning 131
- Nuclear transfer and ESCs 131
- Cloning from differentiated cells 133
- Cloning mice from adult stem cells 133
- Creating interspecies stem cells 134
- Cloned cells for transplantation medicine 134
- Claims of cloning of hESCs 134
- Cytogenetics of embryonic stem cells 136
- Technologies for mobilization, expansion, and engraftment of stem cells
136
- Chemoattraction of neuronal stem cells through GABA receptor 137
- Enhancement of HSC engraftment by calcium-sensing receptor 137
- Ex vivo expansion of human HSCs in culture 137
- Ex vivo expansion of MSCs 138
- Ex vivo expansion of UCB cells for transplantation 138
- Expansion of adult stem cells by activation of Oct4 139
- Expansion of transduced HSCs in vivo 139
- Expansion of stem cells in vivo by Notch receptor ligands 139
- In vivo adipogenesis induced by adipose tissue-derived stem cells 139
- Selective mobilization of progenitor cells from bone marrow 140
- Selective Amplification 140
- Synthetic substrates for ESC growth and expansion 140
- Technologies for inducing differentiation of stem cells 141
- Enhancement of stem cell differentiation by Homspera 141
- Generation of RBCs from HSCs 141
- Generation of multiple types of WBCs from hESCs and iPSCs 141
- Growth factor-induced differentiation of MAPCs 142
- Lineage selection to induce differentiation of hESCs 142
- Mechanical strain to induce MSC differentiation 142
- Neurotrophin-mediated survival and differentiation of hESCs 143
- Synthetic biology and stem cells 143
- Use of RNAi to expand the plasticity of autologous adult stem cells 144
- Use of carbohydrate molecules to induce differentiation of stem cells
144
- Limitations of the currently available stem cell lines in the US 144
- Stem cell separation 145
- Stem cell culture 145
- Culture of hMSCs 146
- Elimination of contaminating material in stem cell culture 146
- Long-term maintenance of MSC multipotency in culture 147
- Nanofiber scaffolds for stem cell culture 148
- Conversion of stem cells to functioning adipocytes 148
- Mass production of ESCs 149
- Promoting survival of dissociated hESCs 149
- Analysis and characterization of stem cells 149
- Havesting and identification of EPCs 150
- Labeling of stem cells 150
- Labeling, imaging and tracking of stem cells in vivo 150
- Perfluorocarbon nanoparticles to track therapeutic cells in vivo 151
- Project for imaging in stem cell therapy research 151
- Quantum dots for labeling and imaging of stem cells 151
- Superparamagnetic iron oxide nanoparticles for tracking MSCs 152
- Applications of stem cells 152
- Commercial development and applications of adult stem cells 153
- Retrodifferentiation of stem cells 153
- MultiStem 153
- Controlling the maintenance process of hematopoietic stem cells 153
- Self renewal and proliferation of HSCs 153
- Aging and rejuvenation of HSCs 154
- Peripheral blood stem cell transplantation 154
- Role of stem cells in regeneration 154
- Promotion of regeneration by Wnt/beta-catenin signaling 155
- Stem cell activation for regeneration by using glucocortoids 155
- Stem cells and human reproduction 156
- Expansion of spermatogonial stem cells 156
- Conversion of ESCs into spermatogonial stem cells 156
- Conversion of stem cells to oocytes 156
- ESCs for treatment of infertility in women 157
- Cloning human embryos from oocytes matured in the laboratory 157
- In utero stem cell transplantation 158
- Innovations in delivery of stem cells 159
- Polymeric capsules for stem cell delivery 159
- Immunological aspects of hESC transplantation 159
- Immunosuppression to prevent rejection of hESC transplants 160
- Histocompatibility of hESCs 160
- Strategies for promoting immune tolerance of hESCs 160
- Stem cells for organ vascularization 161
- Activation of EphB4 to enhance angiogenesis by EPCs 162
- Advantages and limitations of clinical applications of MSCs 162
- Biofusion by genetically engineering stem cells 163
- Stem cell gene therapy 163
- Combination of gene therapy with nuclear transfer 163
- Gene delivery to stem cells by artificial chromosome expression 163
- Genetic manipulation of ESCs 164
- Genetic engineering of human stem cells for enhancing angiogenesis 164
- HSCs for gene therapy 164
- iPSCs for targeted gene correction of α1-antitrypsin deficiency
165
- Helper-dependent adenoviral vectors for gene transfer in ESCs 166
- Lentiviral vectors for in vivo gene transfer to stem cells 166
- Linker based sperm-mediated gene transfer technology 166
- Mesenchymal stem cells for gene therapy 166
- Microporation for transfection of MSCs 167
- Regulation of gene expression for SC-based gene therapy 167
- Stem cells and in utero gene therapy 167
- Therapeutic applications for hematopoietic stem cell gene transfer 168
- The future of hematopoietic stem cell gene therapy 168
- Stem cell pharmaceutics 168
- Pharmaceutical manipulation of stem cells 168
- Antisense approach for preservation and expansion of stem cells 169
- Expansion of HSCs in culture by inhibiting aldehyde dehydrogenase 170
- Manipulation of stem cells with growth factors 170
- Mobilization of stem cells by cytokines/chemokines 173
- Mobilization of adult human HSCs by use of inhibitors 174
- Mobilization of stem cells by HYC750 174
- Mobilization of stem cells by hyperbaric oxygen 174
- Mobilization by adenoviral vectors expressing angiogenic factors 175
- Stem cell mobilization by acetylcholine receptor agonists 175
- Use of parathyroid hormone to increase HSC mobilization 175
- Use of small molecule compounds for expansion of HSCs 176
- Role of stem cells in therapeutic effects of drugs 176
- Stem cells for drug discovery 176
- Target identification 176
- High-throughput screening 177
- Cardiomyocytes derived from hESCs 177
- ESCs as source of models for drug discovery 178
- hESC-derived hepatocytes for drug discovery 178
- Advantages and limitations of use of stem cells for drug discovery 179
- Stem cells for drug delivery 180
- Toxicology and drug safety studies using ESCs versus other cells 180
- Future challenges for stem cell technologies 182
- Study of the molecular mechanism of cell differentiation 183
- MBD3-deficient ESC line 183
- In vivo study of human hemopoietic stem cells 183
- Stem cell biology and cancer 184
- Research into plasticity of stem cells from adults 184
- Stem cells and aging 185
- Activation of bone marrow stem cells into therapeutic cells 186
- Role of nitric oxide in stem cell mobilization and differentiation 186
- Stem cell genes 186
- Gene expression in hESCs 186
- The casanova gene in zebrafish 187
- Nanog gene 187
- Stem cell proteomics 188
- hESC phosphoproteome 189
- Proteomic studies of mesenchymal stem cells 189
- Proteomic profiling of neural stem cells 190
- Proteome Biology of Stem Cells Initiative 190
- Genomic alterations in cultured hESCs 191
- Hybrid embryos/cybrids for stem cell research 191
- Generation of patient-specific pluripotent stem cells 192
- Markers for characterizing hESC lines 192
- Switch of stem-cell function from activators to repressors 193
- Stem cell research at academic centers 193
- International Regulome Consortium 194
- Companies involved in stem cell technologies 195
- Concluding remarks about stem cells 200
- Challenges and future prospects of stem cell research 200
4. Clinical Applications of Cell Therapy 202
- Introduction 202
- Cell therapy for hematological disorders 202
- Transplantation of autologous hematopoietic stem cells 202
- Hemophilias 202
- Ex vivo cell/gene therapy of hemophilia B 202
- Cell/gene therapy of hemophilia A 203
- Hematopoietic stem cell therapy for thrombocytopenia 204
- Stem cell transplant for sickle cell anemia 204
- Treatment of chronic acquired anemias 205
- Implantation of genetically engineered HSCs to deliver rhEpo 205
- Drugs acting on stem cells for treatment of anemia 205
- Stem cell therapy of hemoglobinopathies 206
- Stem cells for treatment of immunoglobulin-light chain amyloidosis 206
- Future prospects of cell therapy of hematological disorders 206
- Cell therapy for immunological disorders 207
- Role of dendritic cells in the immune system 207
- Modifying immune responses of DCs by vaccination with lipiodol-siRNA
mixtures 207
- Potential of MSCs as therapy for immune-mediated diseases 208
- Stem cell therapy of chronic granulomatous disease 208
- Stem cell therapy of X-linked severe combined immunodeficiency 209
- Stem cell therapy of autoimmune disorders 209
- Treatment of rheumatoid arthritis with stem cells 209
- Treatment of Crohn's disease with stem cells 210
- Stem cell transplants for scleroderma 210
- Role of T Cells in immunological disorders 211
- Autologous T cells from adult stem cells 211
- Cell therapy for graft vs host disease 212
- MSCs for GVHD 213
- Cell therapy for viral infections 213
- T-cell therapy for CMV 213
- T-cell therapy for HIV infection 214
- T-cell immunity by Overlapping Peptide-pulsed Autologous Cells 214
- Anti-HIV ribozyme delivered in hematopoietic progenitor cells 215
- Dendritic-cell targeted DNA vaccine for HIV 215
- Cell therapy of lysosomal storage diseases 215
- Niemann-Pick disease 216
- Gaucher's disease 216
- Fabry's disease 217
- Cell therapy for diabetes mellitus 217
- Limitations of current treatment 218
- Limitations of insulin therapy for diabetes mellitus 218
- Limitations of pancreatic transplantation 218
- Islet cell transplantation 219
- Autologous pancreatic islet cell transplantation in chronic pancreatitis
219
- Clinical trials of pancreatic islet cell transplants for diabetes 219
- Drawbacks of islet cell therapy 220
- Use of an antioxidant peptide to improve islet cell transplantation 221
- Cdk-6 and cyclin D1 enhance human beta cell replication and function
221
- A device for delivery of therapeutic cells in diabetes 221
- Monitoring of islet cell transplants with MRI 221
- Concluding remarks about allogeneic islet transplantation for diabetes
222
- Encapsulation of insulin producing cells 222
- Encapsulated porcine pancreatic islet cells for pancreas 222
- Encapsulated insulinoma cells 223
- Magnetocapsule enables imaging/tracking of islet cell transplants 223
- Islet precursor cells 224
- Dedifferentiation of β cells to promote regeneration 224
- Pharmacological approaches for β cell regeneration 225
- Xenotransplantation of embryonic pancreatic tissue 225
- Non-pancreatic tissues for generation of insulin-producing cells 226
- Exploiting maternal microchimerism to treat diabetes in the child 226
- Bio-artificial substitutes for pancreas 226
- Role of stem cells in the treatment of diabetes 227
- Embryonic stem cells for diabetes 227
- HSC transplantation to supplement immunosuppressant therapy 228
- Human neural progenitor cells converted into insulin-producing cells
228
- Insulin-producing cells derived from UCB stem cells 229
- iPS cells for diabetes 229
- Isolation of islet progenitor cells 229
- Pancreatic progenitor cells Expansion in vitro 230
- Pancreatic stem cells 230
- Stem cell injection into portal vein of diabetic patients 230
- Dendritic cell-based therapy for type 1 diabetes 231
- Vaccine for diabetes 231
- Gene therapy in diabetes 231
- Viral vectors for gene therapy of diabetes 232
- Genetically engineered dendritic cells 232
- Genetically altered liver cells 232
- Genetically modified stem cells 233
- Companies developing cell therapy for diabetes 233
- Concluding remarks about cell and gene therapy of diabetes 234
- Cell therapy of gastrointestinal disorders 235
- Inflammatory bowel disease 235
- Cell therapy for liver disorders 236
- Types of cells and methods of delivery for hepatic disorders 236
- Bioartificial liver 237
- Limitations of bioartificial liver 238
- Stem cells for hepatic disorders 238
- Deriving hepatocytes from commercially available hMSCs 239
- Implantation of hepatic cells derived from hMSCs of adipose tissue 239
- Heterologous adult liver progenitor cells 239
- MSC derived molecules for reversing hepatic failure 240
- Cell-based gene therapy for liver disorders 240
- Transplantation of genetically modified fibroblasts 240
- Transplantation of genetically modified hepatocytes 241
- Intraperitoneal hepatocyte transplantation 241
- Genetically modified hematopoietic stem cells 241
- Use of iPSCs derived from somatic cells for liver regeneration 241
- Clinical applications 242
- Future prospects of cell-based therapy of hepatic disorders 242
- Cell therapy of renal disorders 243
- Bioartificial kidney 243
- Cell-based repair for vascular access failure in renal disease 243
- Mesangial cell therapy for glomerular disease 244
- Stem cells for renal disease 244
- Role of stem cells in renal repair 244
- Bone marrow stem cells for renal disease 245
- MSC therapy for renal disease 245
- Cell therapy for pulmonary disorders 245
- Delivery of cell therapy for pumonary disorders 245
- Intratracheal injection of cells for pulmonary hypoplasia 246
- Role of stem cells in pulmonary disorders 246
- Lung stem cells 246
- Lung tissue regeneration from stem cells 246
- Role of stem cells in construction of the Cyberlung 247
- Respiratory epithelial cells derived from UCB stem cells 247
- Respiratory epithelial cells derived from hESCs 247
- Lung tissue engineering with adipose stromal cells 248
- Cell-based tissue-engineering of airway 248
- Pulmonary disorders that can be treatable with stem cells 249
- Acute lung injury and ARDS treated with MSCs 249
- Bronchopulmonary dysplasia treated with MSCs 250
- Chronic obstructive pulmonary disease treated with MSCs 250
- Cystic fibrosis treatment with genetically engineered MSCs 251
- Lung regeneration by integrin α6β4-expressing alveolar
epithelial cell 251
- Pulmonary arterial hypertension treatment with EPCs 251
- Cell therapy for disorders of bones and joints 252
- Repair of fractures and bone defects 252
- Adult stem cells for bone grafting 253
- Cell therapy for osteonecrosis 253
- Cell therapy for cervical vertebral interbody fusion 254
- Cell-mediated gene therapy for bone regeneration 254
- ESCs for bone repair 254
- Intrauterine use of MSCs for osteogenesis imperfecta 254
- In vivo bone engineering as an alternative to cell transplantation 254
- MSCs for repair of bone defects 255
- MSCs for repair of bone fractures 257
- Osteocel 258
- Stem cells for repairing skull defects 258
- Stem cell-based bone tissue engineering 259
- Spinal fusion using stem cell-based bone grafts 260
- Osteoarthritis and other injuries to the joints 260
- Mosaicplasty 261
- Autologous cultured chondrocytes 261
- Autologous intervertebral disc chondrocyte transplantation 262
- Cartilage repair by genetically modified fibroblasts expressing TGF-β
263
- Generation of cartilage from stem cells 263
- Repair of osteonecrosis by bone marrow derived MSCs 264
- Role of cell therapy in repair of knee cartilage injuries 265
- Role of cells in the repair of anterior cruciate ligament injury 266
- Autologous tenocyte implantation in rotator cuff injury repair 267
- Platelet injection for tennis elbow 267
- Cell therapy of rheumatoid arthritis 268
- Cell therapy for diseases of the eye 268
- Cell therapy for corneal repair 268
- Stem cell therapy for limbal stem cell deficiency 270
- Role of stem cells in fibrosis following eye injury 270
- Stem cell transplantation for radiation sickness 271
- MSCs for treatment of radiation damage to the bone 271
- MSCs for regeneration of ovaries following radiotherapy damage 271
- Cell therapy for regeneration 271
- Stem cells for regenerating organs 272
- Umbilical cord blood for regeneration 273
- Role of stem cells in regeneration of esophageal epithelium 273
- Cell therapy for regeneration of muscle wasting 273
- Wound healing: skin and soft tissue repair 274
- Cells to form skin substitutes for healing ulcers 274
- CellSpray for wound repair 275
- Cell therapy for burns 276
- Closure of incisions with laser guns and cells 276
- Follicular stem cells for skin and wound repair 277
- Reprogramming autologous stem cells for wound regeneration 277
- Role of amniotic fluid MSCs in repair of fetal wounds 278
- Genetically engineered keratinocytes for wound repair 278
- MSCs for wound healing 278
- Regeneration of aging skin by adipose-derived stem cells 278
- Repair of aging skin by injecting autologous fibroblasts 279
- Role of cells in tissue engineering and reconstructive surgery 279
- Stem cells for tissue repair 279
- Scaffolds for tissue engineering 279
- Improving vascularization of engineered tissues 280
- Enhancing vascularization by combining cell and gene therapy 280
- Choosing cells for tissue engineering 281
- ESCs vs adult SCs for tissue engineering 281
- Use of adult MSCs for tissue engineering 282
- Nanobiotechnology applied to cells for tissue engineering 282
- Stem cells for tissue engineering of various organs 283
- Engineering of healthy living teeth from stem cells 283
- Adipose tissue-derived stem cells for breast reconstruction 284
- Improving tissue engineering of bone by MSCs 284
- Intra-uterine repair of congenital defects using amniotic fluid MSCs
284
- Cell-based tissue engineering in genitourinary system 285
- Urinary incontinence 285
- Tissue engineering of urinary bladder 286
- Label retaining urothelial cells for bladder repair 287
- MSCs for bladder repair 287
- Tissue-engineering of urethra using autologous cells 287
- Repair of the pelvic floor with stem cells from the uterus 288
- Reconstruction of vagina from stem cells 288
- Facial skin regeneration by stem cells as an alternative to face
transplant 288
- Reconstruction of cartilage for repair of craniofacial defects 289
- Cell therapy for rejuvenation 289
- Cell therapy for performance enhancement in sports 289
- Application of stem cells in veterinary medicine 290
- Use of stem cells to repair tendon injuries 290
- Stem cells for spinal cord injury in dogs 290
5. Cell Therapy for Cardiovascular Disorders 292
- Introduction to cardiovascular disorders 292
- Limitations of current therapies for myocardial ischemic disease 292
- Types of cell therapy for cardiovascular disorders 292
- Cell-mediated immune modulation for chronic heart disease 293
- Human cardiovascular progenitor cells 294
- Inducing the proliferation of cardiomyocytes 294
- Pericardial origin of colony-forming units 295
- Role of the SDF-1-CXCR4 axis in stem cell therapies for myocardial
ischemia 295
- Role of splenic myocytes in repair of the injured heart 295
- Reprogramming of fibroblasts into functional cardiomyocytes 296
- Small molecules to enhance myocardial repair by stem cells 296
- Cell therapy for atherosclerotic coronary artery disease 296
- MyoCell™ (Bioheart) 297
- Cardiac stem cells 297
- Cardiomyocytes derived from epicardium 298
- Methods of delivery of cells to the heart 299
- Cellular cardiomyoplasty 299
- IGF-1 delivery by nanofibers to improve cell therapy for MI 299
- Non-invasive delivery of cells to the heart by MorphRguide catheter 299
- Cell therapy for cardiac revascularization 300
- Transplantation of cardiac progenitor cells for revascularization of
myocardium 300
- Stem cells to prevent restenosis after coronary angioplasty 300
- Role of cells in cardiac tissue repair 301
- Modulation of cardiac macrophages for repair of infarct 301
- Transplantation of myoblasts for myocardial infarction 301
- Patching myocardial infarction with fibroblast culture 302
- Cardiac repair with myoendothelial cells from skeletal muscle 302
- Myocardial tissue engineering 303
- Role of stem cells in repair of the heart 304
- Role of stem cells in cardiac regeneration following injury 304
- Cardiomyocytes derived from adult skin cells 304
- Cardiomyocytes derived from ESCs 304
- Studies to identify subsets of progenitor cells suitable for cardiac
repair 305
- Technologies for preparation of stem cells for cardiovascular therapy
306
- Pravastatin for expansion of endogenous progenitor and stem cells 306
- Cytokine preconditioning of human fetal liver CD133+ SCs 306
- Expansion of adult cardiac stem cells for transplantation 307
- Role of MSCs in growth of CSCs 307
- Role of ESCs in repair of the heart 307
- ESC transplantation for tumor-free repair of the heart 308
- Transplantation of stem cells for myocardial infarction 309
- Autologous bone marrow-derived stem cell therapeutics 309
- Autologous bone marrow-derived mesenchymal precursor stem cells 309
- Transplantation of cord blood stem cells 309
- Transplantation of hESCs 310
- Transplantation of HSCs 310
- Transplantation of autologous angiogenic cell precursors 311
- Transplantation of adipose-derived stem cells 311
- Transplantation of bone marrow-derived cells for myocardial infarct 312
- Intracoronary infusion of mobilized peripheral blood stem cells 313
- Transplantation of endothelial cells 313
- Transplantation of cardiomyocytes differentiated from hESCs 314
- Stem cell therapy for cardiac regeneration 314
- Regeneration of the chronic myocardial infarcts by HSC therapy 314
- Human mesenchymal stem cells for cardiac regeneration 315
- In vivo tracking of MSCs transplanted in the heart 316
- MSCs for hibernating myocardium 316
- Simultaneous transplantation of MSCs and skeletal myoblasts 317
- Transplantation of genetically modified cells 317
- Transplantation of genetically modified MSCs 317
- Transplantation of cells secreting vascular endothelial growth factor
317
- Transplantation of genetically modified bone marrow stem cells 317
- Cell transplantation for congestive heart failure 317
- AngioCell gene therapy for congestive heart failure 318
- Injection of adult stem cells for CHF 319
- Intracoronary infusion of cardiac stem cells 319
- Myoblasts for treatment of congestive heart failure 320
- Stem cell therapy for dilated cardiac myopathy 320
- Role of cell therapy in cardiac arrhythmias 320
- Atrioventricular conduction block 321
- Genetically engineered cells as biological pacemakers 321
- Ventricular tachycardia 322
- Prevention of myoblast-induced arrhythmias by genetic engineering 322
- ESCs for correction of congenital heart defects 323
- Cardiac progenitors cells for treatment of heart disease 323
- Autologus stem cells for chronic myocardial ischemia 324
- Role of cells in cardiovascular tissue engineering 324
- Construction of blood vessels with cells 324
- Engineered arteries for bypass grafts 325
- Fetal cardiomyocytes seeding in tissue-engineered cardiac grafts 325
- Targeted delivery of endothelial progenitor cells labeled with
nanoparticles 325
- UCB progenitor cells for engineering heart valves 325
- Cell therapy for peripheral vascular disease 326
- ALD-301 326
- Cell/gene therapy for PVD 326
- Cell therapy for CLI in diabetics 326
- Colony stimulating factors for enhancing peripheral blood stem cells 327
- Intramuscular autologous bone marrow cells 327
- Ixmyelocel-T cell therapy for critical limb ischemia 327
- Clinical trials of cell therapy in cardiovascular disease 328
- Mechanism of the benefit of cell therapy for heart disease 330
- A critical evaluation of cell therapy for heart disease 331
- Publications of clinical trials of cell therapy for CVD 331
- Current status of cell therapy for cardiovascular disease 332
- Future directions for cell therapy of CVD 332
- Prospects of adult stem cell therapy for repair of heart 333
- Combination of cells with biomedical scaffolds 333
- Regeneration of cardiomyocytes without use of cardiac stem cells 333
6. Cell Therapy for Cancer 336
- Introduction 336
- Cell therapy technologies for cancer 336
- Cell-based delivery of anticancer therapy 337
- Cellular immunotherapy for cancer 337
- Treatments for cancer by ex vivo mobilization of immune cells 338
- Granulocytes as anticancer agents 339
- Neutrophil granulocytes in antibody-based immunotherapy of cancer 339
- Cancer vaccines 339
- Autologous tumor cell vaccines 339
- BIOVAXID 340
- OncoVAX 340
- Tumor cells treated with dinitrophenyl 340
- Vaccines that simultaneously target different cancer antigens 340
- Gene modified cancer cells vaccines 341
- GVAX cancer vaccines 341
- K562/GM-CSF 341
- Active immunotherapy based on antigen specific to the tumor 342
- The use of dendritic cells for cancer vaccination 342
- Autologous dendritic cells loaded ex vivo with telomerase mRNA 342
- Dendritic cell-targeted protein vaccines 343
- Dendritic/tumor cell fusion 343
- Genetically modified dendritic cells 344
- In vivo manipulation of dendritic cells 344
- Preclinical and clinical studies with DC vaccines 344
- Vaccines based on dendritic cell-derived exosomes 345
- Limitations of DC vaccines for cancer 345
- Future developments to enhance clinical efficacy of DC vaccines 345
- Lymphocyte-based cancer therapies 347
- Adoptive cell therapy 347
- Chimeric antigen receptor T cells 348
- Combination of antiangiogenic agents with ACT 349
- Expansion of antigen-specific cytotoxic T lymphocytes 349
- Rescue of CD8+ T cells for use in tumor immunotherapy 350
- Tumor infiltrating lymphocytes 350
- Genetic engineering of tumor cells to activate T helper cells 350
- Hybrid cell vaccination 351
- Chemoimmunotherapy 351
- Stem cell-based anticancer therapies 352
- Stem cell transplantation in cancer 352
- Peripheral blood stem cell transplantation 352
- Stem cell transplantation for hematological malignancies 354
- Long-term results of HSC transplantation 355
- Prediction of T-cell reconstitution after HSC transplantation. 355
- HSC transplantation followed by GM-CSF-secreting cell vaccines 356
- HSC transplantation for renal cell cancer 356
- Complications of stem cell transplants in cancer 356
- Graft-versus-host disease (GVHD). 356
- Delayed immune reconstitution leading to viral infections and relapse
357
- Tumor cell contamination 357
- Neurological complications 358
- Hepatic veno-occlusive disease 358
- Current status of the safety of allogeneic HSC transplantation 358
- Complications of PBSC transplantation in children 359
- Role of MSCs in cancer 359
- MSC-mediated delivery of anticancer therapeutics 359
- Nonmyeloablative allogeneic hematopoietic stem cell transplantation 360
- Umbilical cord blood transplant for leukemia 361
- hESC-derived NK cells for treatment of cancer 361
- ESC vaccine for prevention of lung cancer 361
- Genetic modification of stem cells for cancer therapy 362
- Genetic modification of hematopoietic stem cells 362
- Use of hematopoietic stem cells to deliver suicide genes to tumors 362
- Delivery of anticancer agents by genetically engineered MSCs 362
- Mesenchymal progenitor cells for delivery of oncolytic adenoviruses 363
- Genetically modified NSCs for treatment of neuroblastoma 363
- Innovations in cell-based therapy of cancer 364
- Use of immortalized cells 364
- Cancer therapy based on natural killer cells 364
- Cytokine-induced killer cells 365
- Mesothelin as a target for cancer immunotherapy 365
- Nanomagnets for targeted cell-based cancer gene therapy 365
- Implantation of genetically modified encapsulated cells for anticancer
therapy 366
- Antiangiogenesis therapy by implantation of microencapsulated cells 366
- Recombinant tumor cells secreting fusion protein 366
- NovaCaps&rec; for pancreatic cancer 366
- A device for filtering cancer and stem cells in the blood 366
- Cancer stem cells 367
- Role of integrative nuclear signaling in stem cell development 367
- Cancer stem cell markers 368
- Breast cancer stem cells 368
- Role of intestinal stem cells in intestinal polyposis 369
- Role of endothelial progenitor cells in tumor angiogenesis 369
- Role of cancer stem cells in metastases 369
- Therapeutic implications of cancer stem cells 369
- Targeting cancer stem cells in leukemia 370
- Targeting stem cells in ovarian cancer 371
- Targeting cancer stem cells to screen anticancer drugs 371
- Cell-based therapies for malignant brain tumors 371
- Bone morphogenetic protein for inhibition of glioblastoma multiforme 372
- Dendritic cell therapy for brain tumors 372
- Encapsulated cells for brain tumors 373
- Immunotherapy of GBM targeting cancer stem cells 373
- Mesenchymal stem cells for the treatment of gliomas 374
- Neural stem cells for drug/gene delivery to brain tumors 374
- Role of cancer stem cells in resistance to radiotherapy 375
- Targeting stem cells in brain tumors 376
- Companies involved in cell-based cancer therapy 376
- American Association for Cancer Research and ESCs 377
- Future of cell-based immunotherapy for cancer 378
7. Cell Therapy for Neurological Disorders 380
- Introduction 380
- Regeneration of the nervous system by endogenous stem cells 380
- Molecular mechanism of neurogenesis 380
- Generation of neurons from astroglia 381
- In vivo cell replacement therapy by locally induced neural progenitor
cells 381
- Types of cells used for treatment of neurological disorders 382
- Activated T lymphocytes 382
- Differentiation of placenta-derived multipotent cells into neurons 382
- Mesenchymal stem cells induced to secrete neurotrophic factors 383
- Neural stem cells 383
- Development of human CNS stem cells 383
- Distinction between NSCs and intermediate neural progenitors 384
- Embryonic stem cell-derived neurogenesis 384
- Induction of NSCs fro hESCs 385
- Mechanism of migration of neural stem cells to sites of CNS injury 386
- Monitoring of implanted NSCs labeled with nanoparticles 386
- Neural progenitor cells 387
- Neural stem cells as therapeutic delivery vehicles 388
- Neural stem cells in the subventricular zone of the brain 389
- Oligodendrocyte progenitor cells 389
- Promotion of neural stem cells expansion by betacellulin 389
- Proteomics of neural stem cells 389
- Regulation of neural stem cells in the brain 390
- Role of CSF proteins in regulation of neural progenitor cells 391
- Sequencing the transcriptomes of neural stem cells 391
- Study of neural differentiation of hESCs by NeuroStem Chip 391
- Transformation of neural stem cells into other cell types 392
- Use of epidermal neural crest stem cells for neurological disorders 392
- Olfactory epithelium stem cells for transplantation in the CNS 392
- Development of CNS cells from non-CNS stem cells 392
- Derivation of CNS cells from peripheral nervous system 393
- Hair-follicle stem cells for neural repair 394
- Stem cells from human umbilical cord blood for CNS disorders 394
- Immortalized cells for CNS disorders 394
- Fetal tissue transplants 395
- Choroid plexus cells 396
- Laboratory mice with human brain cells 396
- Expansion of adult human neural progenitors 396
- Neurospheres 397
- Dental pulp cells for neuroprotection 397
- Ideal cells for transplantation into the nervous system 397
- Cell therapy techniques for neurological applications 398
- Carbon nanotubes to aid stem cell therapy of neurological disorders 398
- Cells used for gene therapy of neurological disorders 398
- Fibroblasts 398
- Stem cells 399
- Neuronal cells 399
- Immortalized neural progenitor cells 399
- Astrocytes 400
- Cerebral endothelial cells 400
- Human retinal pigmented epithelial cells 401
- Enhancement of growth of stem cells in the brain by drugs 401
- C3-induced differentiation and migration of NPC for repair of the brain
402
- Stem cell therapies of neurological disorders combined with HBO 402
- hESCs for CNS repair 402
- Methods of delivery of cells to the CNS 403
- Engineered stem cells for drug delivery to the brain 403
- Neuronal differentiation of stem cells 404
- Stem cells preparations for CNS disorders 404
- Tracking of stem cells in the CNS by nanoparticles and MRI 405
- Use of neural stem cells to construct the blood brain barrier 406
- Encapsulated cells 406
- CNS neotissue implant 406
- Intrathecal delivery of stem cells 407
- CNS delivery of cells by catheters 408
- Intravascular administration 408
- Neurological disorders amenable to cell therapy 408
- Neuroprotection by cell therapy 409
- Cells secreting neuroprotective substances 409
- Stem cells for neuroprotection 409
- Neuroprotection by intravenous administration of HSCs 409
- Human UCB-derived stem cells for the aging brain 410
- hESC transplantation to prevent cognitive impairment from radiation 410
- Neurodegenerative disorders 410
- Role of stem cells in neurodegenerative disorders 410
- MSCs for therapy of neurodegenerative disorders 411
- Role of NSCs in disorders associated with aging brain 412
- NSCs for improving memory 413
- Parkinson's disease 413
- Origin and fate of dopamine neurons 414
- Human dopaminergic neurons for PD 415
- Graft survival-enhancing drugs 415
- Xenografting porcine fetal neurons 416
- Encapsulated cells for PD 416
- Stem cells for PD 416
- Stem cells for production of glial derived neurotrophic factor 419
- Potential of regeneration of endogenous stem cells in PD 419
- Human retinal pigment epithelium cells for PD 419
- Coaxing hESCs to produce dopamine 420
- Tumorigenic potential of transplantated dopaminergic hESCs 420
- Transplantation of embryonic medial ganglionic eminence cells 420
- Delivery of cells for PD 421
- MSCs for multiple system atrophy 421
- Cell therapy for Huntington's disease 422
- Fetal striatal cell transplantation 422
- Transplantation of encapsulated porcine choroids plexus cells 422
- Cell therapy for Alzheimer's disease 423
- Neural stem cell implantation for Alzheimer's disease 423
- Implantation of genetically engineered cells producing NGF 423
- Cell therapy for amyotrophic lateral sclerosis 424
- Stem cell techniques for study of ALS 424
- Use of stem cells for ALS 425
- Transplantation of glial restricted precursors in ALS 426
- Stem cell-based drug discovery for ALS 427
- Cell therapy for demyelinating disorders 427
- Autologous bone marrow stem cell therapy for MS 428
- ESCs for remyelination 428
- Fusokine method of personalized cell therapy of MS 428
- Hematopoietic stem cell transplantation for MS 429
- Mechanism of repair of demyelination after NSC transplantation 429
- Neural progenitor cells for neuroprotection in MS 430
- T cell-based personalized vaccine for MS 430
- Stem cells for chronic inflammatory demyelinating polyneuropathy 431
- X-linked adrenoleukodystrophy 431
- Cell therapy of stroke 431
- Adult stem cell therapy in stroke 432
- Implantation of genetically programmed ESCs 432
- Intravenous infusion of MSCs 433
- Intravenous infusion of human UCB stem cells 433
- Intracerebral administration of human adipose tissue stromal cells 434
- Neural stem cell therapy for stroke 434
- Transplantation of encapsulated porcine choroids plexus 435
- Transplantation of fetal porcine cells 436
- Role of cell therapy in management of stroke according to stage 436
- Clinical trials of cell therapy for stroke 436
- Future of cell therapy for stroke 438
- Cell therapy of traumatic brain injury 439
- Cell/gene therapy for TBI 439
- Clinical trials of autologous HSC therapy for TBI 439
- Limitations of stem cell therapy for acute TBI 440
- Improving the microenvironments of transplanted cells in TBI 440
- Cell therapy for spinal cord injury 441
- Autoimmune T cells against CNS myelin-associated peptide 441
- Fetal neural grafts for SCI 441
- Olfactory-ensheathing cells for SCI 441
- Oligodendrocyte precursor cells for treatment of SCI 442
- Schwann cell transplants for SCI 442
- Transplantation of glial cells for SCI 442
- Stem cells for SCI 443
- Bone marrow stem cells for SCI 443
- Embryonic stem cells for SCI 443
- Transplantation of induced pluripotent stem cells in SCI 444
- Transplantation of MSCs for SCI 444
- Transplantation of NSCs for SCI 445
- Transplantation of human dental pulp stem cells 445
- Transdifferentiation of BM stem cells into cholinergic neurons for SCI
446
- Spinal stem cells for treatment of ischemic injury of spinal cord 446
- Combined approaches for regeneration in SCI 446
- Combined cell/gene therapy for SCI 447
- Delivery of cells in SCI 447
- Intrathecal injection of cells labeled with magnetic nanoparticles 447
- Intravenous injection of stem cells for spinal cord repair 448
- Clinical applications of stem cells for SCI 448
- Autologous bone marrow cell transplantation for SCI 448
- Cell therapy of syringomyelia 448
- Cell therapy for neurogenetic disorders 449
- Hurler's syndrome treated with stem cells 449
- Krabbe's disease treated with UCB stem cells 449
- Krabbe's disease treated with combination of cell and gene therapy 450
- Mitochondrial encephalomyopathies treated with stem cells 450
- Sanfilippo syndrome type B treated with UCB stem cells 451
- Cell therapy for lysosomal storage disorders 451
- Cell therapy for Batten disease 451
- Cell/gene therapy for Farber's disease 452
- Genetically modified HSCs for metachromatic leukodystrophy 452
- Neural stem cells for lysosomal storage disorders 453
- Cell therapy of epilepsy 453
- Cell therapy of posttraumatic epilepsy 453
- Cell therapy for temporal lobe epilepsy 454
- Cell therapy for pharmacoresistant epilepsies 454
- Cell therapy for developmental neurological disorders 454
- Cell therapy for cerebral palsy 455
- Cell therapy for muscle disorders 455
- Duchenne muscular dystrophy 455
- Combination of cell and pharmacotherapy for DMD 456
- Myoblast transplant for DMD 456
- Myoblast-based gene transfer 457
- Myoblasts lacking the MyoD gene 457
- Myoblast injection for treatment of other muscular dystrophies 457
- Role of satellite cells in the treatment of DMD 458
- Stem cells for DMD 458
- Cell therapy for Autism 460
- Management of chronic intractable pain by cell therapy 460
- Implantation of chromaffin cells 461
- Role of stem cells in management of pain 461
- Implantation of astrocytes secreting enkephalin 461
- Cells for delivery of antinociceptive molecules 462
- Implantation of genetically engineered cells 462
- Cell therapy for low back pain 462
- Cell therapy for neuroendocrine disorders 463
- Pituitary stem cells 463
- Cell therapy for retinal degenerative disorders 463
- Human retinal stem cells 464
- Delivery of CNTF by encapsulated cell intraocular implants 465
- Stem cell transplantation in the retina 465
- ESCs for retinal degenerative disorders 466
- hESC-derived RPE cells for macular dystrophy 466
- Neuroprotective effect of neural progenitor cell transplantation 466
- Genetically engineered retinal pigmented epithelial cell lines 467
- Combining cell and gene therapies for retinal disorders 467
- Stem cell therapy for hearing loss 467
- Cell thery for peripheral nerve lesions 468
- Cell transplants for peripheral nerve injuries 468
- Treatment of diabetic neuropathy with endothelial progenitor cells 468
- Complications of cell therapy of CNS disorders 468
- Tumor formation after CNS transplantation of stem cells 468
- Uncontrolled differentiation of implanted cells 468
- Donor stem cell-derived brain tumor 469
- Clinical trials of cell therapy in neurological disorders 469
- Future prospects for cell therapy of CNS disorders 470
8. Ethical and Political Aspects of Cell therapy 472
- Introduction 472
- Political and ethical aspects of hESC research in the US 472
- Ethical issues concerning fetal tissues 472
- Morality and hESC research 472
- Opponents of hESC research in the US 473
- Use of hESCs in NIH-supported research 474
- Politics of hESC research in the US 475
- Public opinion in the US about hESC research 477
- Human stem cell cloning in the US 478
- Stem cell guidelines of various US institutions 479
- Ethics of transplanting human NSCs into the brains of nonhuman primates
479
- Stem cell lines available worldwide 480
- Stem cell policies around the world 481
- Countries with no defined policies on hESC research 481
- Australia 482
- Canada 482
- China 483
- Denmark 484
- France 484
- Germany 484
- India 486
- Ireland 487
- Israel 487
- Italy 487
- Japan 488
- The Netherlands 488
- Saudi Arabia 489
- Singapore 489
- South Africa 489
- South Korea 490
- Spain 490
- Sweden 490
- Switzerland 491
- United Kingdom 491
- ESC bank 492
- European Union 493
- EU guidelines for stem cell research 493
- EMBO's recommendations for stem cell research 494
- Public opinion in Europe about hESC research 495
- United Nations, cloning and nuclear transfer 496
- The Embryo Project for information on ESC research 497
- Concluding remarks about ethics of ESC research 497
- Ethical issues concerning umbilical cord blood 497
- Cell therapy tourism 498
9. Safety and Regulatory Aspects of Cell Therapy 500
- Introduction 500
- Safety issues of cell therapy 500
- Immune-mediated reactions to transpanted stem cells 500
- Human virus infections associated with stem cell transplantation 501
- Herpes simplex virus type 1 501
- Cytomegalovirus 501
- Opportunistic infections among hematopoietic stem cell transplant
recipients 501
- Cord colitis syndrome 501
- Carcinogenic potential of stem cells and its prevention 502
- FDA safety regulations for cell and tissue products 502
- FDA Guidance on license applications for umbilical cord blood products
503
- Regulation of cord blood banks in the US 503
- Regulatory issues for biotechnology-derived drugs 503
- Regulation of cell selection devices for PBSCs at point of care 504
- FDA rules for human cells and tissues 505
- FDA regulation of fetal cellular or tissue products 505
- FDA and clinical trials using hESCs 506
- Cell and gene therapy INDs placed on hold by the FDA 506
- Regulatory issues for genetically engineered cell transplants 507
- FDA guidelines for human tissue transplantation 507
- Xenotransplantation 507
- Clinical Protocol Review and Oversight 508
- Informed consent and patient education 508
- Xenotransplantation product sources 508
- FDA guidelines for xenografts 509
- Regulations relevant to cell therapy in the European Union 510
- Regulations about use of stem cells in the EU 511
- EMEA regulation of cell/gene therapy 511
- Guidelines for cell therapy in the UK 512
- NIH and stem cells 513
- hESC lines approved under the new NIH guidelines 513
- Clinical trials in cell therapy 514
- Stem cell patents 514
- Stem cell patents in the United States 514
- Current status of Thomson patents at WARF 515
- Stem cell patents in the European Union 515
Tables
- Table 1-1: Landmarks in the history of cell therapy 28
- Table 1-2: Examples of cells involved in various diseases 33
- Table 2-1: Types of human cells used in cell therapy 36
- Table 2-2: A selection of companies providing cell culture media 40
- Table 2-3: A sampling of companies supplying cell sorters 45
- Table 2-4: Companies involved in cell-based drug discovery 52
- Table 2-5: Methods of delivery of cells for therapeutic purposes 54
- Table 2-6: Therapeutic applications of encapsulated cells 58
- Table 2-7: Companies working on encapsulated cell technology 60
- Table 2-8: Molecular imaging methods for tracking cells in vivo 66
- Table 3-1: Companies involved in cord blood banking as a source of stem
cells 102
- Table 3-2: Sources of adult human stem cells 112
- Table 3-3: Comparison of human stem cells according to derivation 122
- Table 3-4: Enhancing engraftment, mobilization and expansion of stem cells
136
- Table 3-5: Applications of stem cells 152
- Table 3-6: Advantages and limitations of methods for optimizing MSCs
162
- Table 3-7: Growth factors with positive effects on stem cells and
applications 170
- Table 3-8: Examples of drugs that induce granulocytopenia at stem cell
level 181
- Table 3-9: Academic institutes involved in stem cell research 193
- Table 3-10: Companies involved in stem cell technologies 195
- Table 4-1: Therapeutic applications of regulatory T cells (T-regs) 211
- Table 4-2: Various tissue/cell therapy approaches to the treatment of type
1 diabetes 217
- Table 4-3: Companies involved in cell therapy for insulin-dependent
diabetes 233
- Table 4-4: Major pulmonary disorders potentially treatable by stem cell
manipulation 249
- Table 4-5: Cell-based repair of knee cartilage damage 265
- Table 5-1: Classification of various types of cell therapy for
cardiovascular disorders 292
- Table 5-2: Clinical trials of cell therapy in cardiovascular disease
328
- Table 6-1: Cell therapy technologies used for cancer 336
- Table 6-2: Companies involved in developing cell-based therapies for
cancer 376
- Table 7-1: Experimental use of immortalized cells for CNS disorders
394
- Table 7-2: Combination of stem cells and HBO in models of neurological
disorders 402
- Table 7-3: Methods for delivering cell therapies in CNS disorders 403
- Table 7-4: Neurological disorders amenable to cell therapy 408
- Table 7-5: Types of cell used for investigative treatment of Parkinson's
disease 413
- Table 7-6: Status of cell therapies for Parkinson's disease 414
- Table 7-7: Role of cell therapy in management of stroke according to stage
436
- Table 7-8: Clinical trials of cell therapy for stroke: completed, ongoing
and pending 436
- Table 7-9: Clinical trials with cell-based therapies in neurological
disorders (excluding stroke) 469
- Table 8-1: Listed numbers of stem cell lines around the world as of end of
2008 480
- Table 8-2: Stem cell policies around the world 481
- Table 8-3: European public attitudes about research involving human stem
cells 496
- Table 9-1: Possible adverse reactions and safety issues of cell therapy
500
Figures
- Figure 1-1: Interrelationships of cell therapy to other technologies
30
- Figure 1-2: Interrelationships of gene, cell and protein therapies 32
- Figure 3-1: A simplified biological scheme of embryonic stem Cells 73
- Figure 3-2: Steps of iPS cell production 106
- Figure 3-3: Flow chart of development of stem cells with potential
bottlenecks 200
- Figure 5-1: hESC-derived cardiomyocytes from laboratory to bedside 305
- Figure 6-1: A scheme of generation and administration of tumor
antigen-pulsed dendritic cells 346
- Figure 6-2: Stem cell transplantation techniques 353
- Figure 7-1: Stem cells that can give rise to neurons 388
- Figure 7-2: Approaches to stem cell therapy in stroke 432
Part II
10. Markets and Future Prospects for Cell Therapy 5
- Introduction 5
- Methods for estimation of cell therapy markets 5
- Potential markets for cell therapy 6
- Markets according to technologies 6
- Stem cell transplant 6
- Supporting cell technologies 6
- Blood transfusion market 7
- Cord blood collection and storage 7
- Cell therapy and related technologies 7
- Cell therapy markets according to therapeutic area 7
- Bone and joint disorders 8
- Cancer 8
- Cardiovascular disorders 8
- Diabetes mellitus 9
- Liver disorders 10
- Neurological disorders 10
- Retinal degenerative diseases market 11
- Skin and wound care 11
- Urinary incontinence 11
- Reconstruction of teeth by stem cell implants 11
- Market size according to geographical areas 12
- Unmet market needs in cell therapy 12
- Drivers of growth of cell therapy markets 13
- Role of stem cells in regenerative medicine 13
- Role of cells in markets for artificial organs 14
- Increase of R&D expense on cell therapy 14
- Increased used of cell-based drug discovery 14
- Impact of emerging healthcare trends on cell therapy markets 14
- Markets for cell therapy tourism 14
- Future prospects of cell therapy 15
- Embryonic stem cell research around the world 15
- Consortia for ESC research in Europe 15
- EuroStemCell 15
- FunGenES 16
- ESTOOLS 17
- UK National Stem Cell Network 18
- Ethical concerns about commercialization of embryonic stem cells 18
- Education of the physicians 18
- Public education 19
- NIH support of stem cell research 19
- Funding of stem cell research from non-federal sources 19
- Prospects of venture capital support for stem cell companies 21
- Cell therapy in the developing countries 21
- Guidelines for stem cell therapies 22
- Business strategies 23
- Formation of networks 23
- Future market potential of adult vs embryonic stem cells 24
11. Companies Involved in Cell Therapy 25
- Introduction 25
- Profiles of selected companies 27
- Collaborations 334
12. Academic Institutions 343
- Introduction 343
- Stem cell center 343
- Profiles of institutions 344
- Collaborations 428
13. References 431
Tables
- Table 10-1: Market size according to cell therapy and related technologies
2011-2021 6
- Table 10-2: Market size according to therapeutic areas for cell therapy
2011-2021 7
- Table 10-3: Cell therapy markets for cardiovascular disorders 2011-2021
9
- Table 10-4: Values of cell therapies for neurological disorders 2011-2021
10
- Table 10-5: Total cell therapy market according to geographical areas
2011-2021 12
- Table 10-6: Cord blood market according to geographical areas 2011-2021
12
- Table 10-7: Stem cells transplant market according to geographical areas
2011-2021 12
- Table 11-1: Publicly traded cell therapy companies 25
- Table 11-2: Selected collaborations of cell therapy companies 334
- Table 12-1: Therapeutic uses of stem cells 351
- Table 12-2: Commercial collaborations of US academic institutes relevant
to stem cells 428
Figures
- Figure 10-1: Unmet needs in cell therapy 13
